鸡TLRs基因的表达调控与抗沙门氏菌的机制研究
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摘要
Toll样受体（TLRs）信号通路诱导的先天免疫反应是宿主抵抗沙门氏菌感染的第一道防线。沙门氏菌感染鸡后，正常状态下，鸡体内的TLRs信号传递会迅速激活，但是抗病鸡抵抗沙门氏菌和感病鸡不能抵抗沙门氏菌的确切机制目前并不清楚。本文首先在细胞水平上研究LPS刺激和肠炎沙门氏菌（SE）感染鸡细胞后TLRs家族基因的表达情况，然后在活体水平用SE对SPF鸡攻毒，研究参与防御SE的几个重要的TLRs基因的表达情况以及可能存在的TLRs基因调控和被调控的分子机制。全文共包括3个试验：
试验一：LPS刺激/沙门氏菌感染鸡单个核细胞中TLRs家族基因的表达变化规律。从20只30日龄SPF中分离外周血单个核细胞（PBMCs），设计LPS刺激、肠炎沙门氏菌感染诱导和对照组三个处理，研究诱导后1h、6h和24h不同时间点细胞中9个TLRs基因的表达变化，并用1×10~9～1×10~4CFU10倍剂量梯度稀释的SE感染鸡PBMCs6h，进一步验证不同剂量SE感染诱导对参与防御SE的三个重要的TLRs基因—TLR4、TLR2-1和TLR21表达的影响。结果表明：（1）LPS刺激和沙门氏菌感染均能上调7个TLRs基因的表达，包括TLR4、TLR21和TLR2-1等重要识别受体基因。（2）诱导后6h，LPS处理组中TLR4和TLR2基因的表达显著上调（P <0.05），表达量为对照组的2倍以上。而沙门氏菌感染组TLR4的表达与对照组相比显著下调（P <0.05），TLR21和TLR2的表达量则没有显著变化（P>0.05）。（3）诱导后24h，沙门氏菌感染组TLR21和TLR1-2上调表达的倍数显著高于LPS处理组（P <0.05）；而TLR4、TLR2(TLR2-1和TLR2-2)和TLR1-1等基因在LPS处理组上调程度显著高于沙门氏菌感染组（P <0.05）。（4）不同剂量的SE感染细胞后6h，TLR4、TLR21和TLR2-1的表达或显著下调（P <0.05）或表达差异不显著（P>0.05）（1×10~9CFU的SE感染时TLR2-1的表达量除外），SE的感染剂量会影响表达下调的程度。感染剂量为0～1×106CFU时，增加沙门氏菌的剂量，TLRs基因表达抑制作用增强；而感染剂量为1×10~6～1×10~9CFU时，随SE感染剂量的增加，TLRs基因表达抑制作用减弱。
试验二：抗病组和感病组鸡中TLRs、炎症因子及TLRs负调控基因的表达差异。为了研究TLRs的表达与鸡对沙门氏菌的抗、感病机制的关系，用8.7×10~8CFU的SE对20只30日龄的SPF鸡进行攻毒，攻毒后5日内死亡的鸡定为感病组，存活了15日的鸡定为抗病组，两组鸡各6只，比较攻毒后0h、8h、16h、24h、3d、12d的载菌量及基因表达的差异。结果表明：（1）16h感病组血液中肠炎沙门氏菌的载菌量为1.1×107CFU，显著高于抗病组（P <0.05）。（2）16h抗病组鸡的体温42.6℃显著高于攻毒前0h的体温41.9℃（P <0.05），而感病鸡体温的增加没有达到显著（P>0.05）；3d时感病鸡的体温41.1℃显著低于抗病鸡的体温42.3℃（P <0.05）。（3）感病组鸡体重自16h持续下降，而抗病组16h后体重增加；在3d时感病组体重212.7g显著低于抗病组体重252.9g（P <0.05）。（4）感病鸡白细胞中TLR4、TLR2-1和TLR21的表达量显著低于抗病组（P <0.05）。（5）IFN-β和促炎症因子IL-6的基因表达量在抗病鸡中显著高于感病组（P<0.05）。（6）负调控基因ZNF493和TOLLIP仅在感病鸡中显著上调表达（P <0.05）。以上结果表明：TLRs基因的表达受到抑制导致炎症因子表达不足、载菌量增加、体重下降是感病组鸡死亡的主要原因。
试验三：表观遗传修饰对TLRs基因的表达调控。为深入研究感病鸡中SE感染后16h时TLRs的表达抑制是否与ZNF493依赖的表观调控相关，在细胞水平研究了甲基化酶和去乙酰化酶抑制剂对鸡单个核细胞TLRs的表达变化；并用重亚硫酸盐修饰后测序PCR（BSP）方法比较了感病组和抗病组鸡中TLR4、TLR21和TLR2-1基因启动子区域以及外显子区域的CpG岛的甲基化水平。结果表明：（1）在沙门氏菌感染的外周血单个核细胞中，甲基化酶抑制剂5-Aza-dc处理均可以显著增加TLR4的表达（P <0.05），5-Aza-dc和TrichostatinA都可以显著上调TLR21和TLR2-1的表达（P <0.05），但两者没有协同效应。（2）感病组鸡TLR4和TLR21启动子区域、TLR2-1的外显子CpG岛区域的甲基化程度显著高于抗病鸡（P <0.05）。结果表明：TLR4、TLR21和TLR2-1的表达受甲基化调控，感病鸡中TLR4、TLR21和TLR2-1的表达抑制可能由于过高的甲基化引起。
总体而言，本研究结果表明TLRs家族中TLR4、TLR21和TLR2-1是肠炎沙门氏菌感染的重要识别受体，鸡白细胞中TLR4、TLR21和TLR2-1的表达被抑制是导致沙门氏菌易感性增加、鸡死亡的主要原因，而ZNF493相关的表观修饰促使TLRs表达被抑制。
Toll-like receptors (TLRs) signaling pathways are the first lines in defense against Salmonellainfection. Ordinarily, TLRs signaling is activated immediately when chickens infected with Salmonella,but the molecular mechanism underlying susceptibility to S. enteritidis infection in chickens remainsunclear. This research included three sections:
Section1: The transcriptional regulation of TLRs in peripheral blood mononuclear cells (PBMCs) ofchickens infected in vitro with LPS or Salmonella. PBMCs were segregated from20specific-pathogen-free (SPF) chickens with30d old. Three treatments including LPS treatment,Salmonella enteritidis (S. enteritidis) infection and control groups were designed. The expression of9TLRs at1h,6h and24h post infection in PBMCs were investigated. In order to verify the effect of S.enteritidis infection dose on the expression of TLR4, TLR2-1and TLR21, PBMCs infected with S.enteritidis with1×10~9to1×10~4CFU with10folds dilution for6h. The results are as follow:(1)Expression of9TLRs including TLR4, TLR2-1and TLR21in PBMCs were upregulated by LPS orSalmonella.(2) At6h, expression of TLR4and TLR2were significantly upregulated in LPS treatmentgroup (P <0.05), but expression of TLR4was significantly downregulated compared with that ofcontrol (P <0.05), there was not significant change of expression of TLR21and TLR2(P>0.05). At24h, the upregulation of TLR21and TLR1-2was greater in Salmonella-treated group while thetranscription of TLR4, TLR1-1, TLR2(TLR2-1and TLR2-2) increased more significantly in LPS group(P <0.05).(4) The expression of TLR4, TLR21and TLR2-1decreased with different concentration ofSalmonella treatment. The depression of TLRs enhanced with the increase of concentration in the caseof low concentration (0～1×10~6CFU/mL) of Salmonella but go to the opposite direction in highconcentration (1×10~6～1×10~9CFU/mL).
Section2: The effect of transcriptional regulation of TLRs, pro-inflammatory genes and negativeregulators of TLRs on the susceptibility to Salmonella in Chickens. This section aimed to demonstratethe molecular mechanism underlying susceptibility to S. enteritidis infection. SPF chickens injectedwith8.7×108CFU of S. enteritidis were partitioned into two groups, one consisted of those fromSalmonella-susceptible chickens (died within5d after injection, n=6), the other consisted of sixSalmonella-resistant chickens that survived for15d after injection. The results showed that:(1) Thepresent study showed that the bacterial load1.1×10~7CFU in susceptible chickens was significantlyhigher than that in resistant chickens at16h post infection (P <0.05).(2) Temperature of resistantchickens with42.6℃at16h was significantly higher than41.9℃at0h (P <0.05), but the increase oftemperature in susceptible chickens was not significant (P>0.05); The temperature of susceptiblechickens with41.1℃on3d was significantly lower than that of resistant chickens with42.3℃(P <0.05). Body weight of susceptible chickens decreased after16h but that of resistant chickens increased;Body weight of susceptible chickens with212.7g was significantly lower than that of resistant chickenswith252.9g (P <0.05).(4) Expression of TLR4, TLR2-1and TLR21was strongly diminished in theleukocytes of susceptible chickens compared with those of resistant chickens (P <0.05).(5) The induction of expression of IFN-β and pro-inflammatory cytokine genes like IL-6, was greatly enhancedin the resistant chickens but not in susceptible chickens (P <0.05).(6) Contrasting with the reducedexpression of TLRs genes, which of the zinc finger protein493(ZNF493) gene and Toll-interactingprotein (TOLLIP) gene were enhanced in the susceptible chickens.
Section3: The role of epigenetic regulation in the depressed transcription of TLRs in susceptiblechickens. The main task of this section was to confirm whether ZNF493-related epigenetic modificationaccounted for the diminished expression of TLRs in susceptible chickens. The results demonstrated that:(1) The expression of TLR4in peripheral blood mononuclear cells (PBMCs) infected in vitro with S.enteritidis increased significantly as a result of treatment with5-Aza-2-deoxycytidine (5-Aza-dc) ortrichostatin A (TSA) while either5-Aza-dc or TSA was effective in up-regulating the expression ofTLR21and TLR2-1.(2) DNA methylation, in the predicted promoter and proximal promoter region ofTLR4and TLR21genes, and an exonic CpG island of the TLR2-1gene was significantly higher in thesusceptible chickens than that in resistant chickens. Taken together, the results demonstrate thatZNF493-related epigenetic modification in leukocytes probably accounts for increased susceptibility toS. enteritidis in chickens by diminishing the expression and response of TLR4, TLR21and TLR2-1.
试验一：LPS刺激/沙门氏菌感染鸡单个核细胞中TLRs家族基因的表达变化规律。从20只30日龄SPF中分离外周血单个核细胞（PBMCs），设计LPS刺激、肠炎沙门氏菌感染诱导和对照组三个处理，研究诱导后1h、6h和24h不同时间点细胞中9个TLRs基因的表达变化，并用1×10~9～1×10~4CFU10倍剂量梯度稀释的SE感染鸡PBMCs6h，进一步验证不同剂量SE感染诱导对参与防御SE的三个重要的TLRs基因—TLR4、TLR2-1和TLR21表达的影响。结果表明：（1）LPS刺激和沙门氏菌感染均能上调7个TLRs基因的表达，包括TLR4、TLR21和TLR2-1等重要识别受体基因。（2）诱导后6h，LPS处理组中TLR4和TLR2基因的表达显著上调（P <0.05），表达量为对照组的2倍以上。而沙门氏菌感染组TLR4的表达与对照组相比显著下调（P <0.05），TLR21和TLR2的表达量则没有显著变化（P>0.05）。（3）诱导后24h，沙门氏菌感染组TLR21和TLR1-2上调表达的倍数显著高于LPS处理组（P <0.05）；而TLR4、TLR2(TLR2-1和TLR2-2)和TLR1-1等基因在LPS处理组上调程度显著高于沙门氏菌感染组（P <0.05）。（4）不同剂量的SE感染细胞后6h，TLR4、TLR21和TLR2-1的表达或显著下调（P <0.05）或表达差异不显著（P>0.05）（1×10~9CFU的SE感染时TLR2-1的表达量除外），SE的感染剂量会影响表达下调的程度。感染剂量为0～1×106CFU时，增加沙门氏菌的剂量，TLRs基因表达抑制作用增强；而感染剂量为1×10~6～1×10~9CFU时，随SE感染剂量的增加，TLRs基因表达抑制作用减弱。
试验二：抗病组和感病组鸡中TLRs、炎症因子及TLRs负调控基因的表达差异。为了研究TLRs的表达与鸡对沙门氏菌的抗、感病机制的关系，用8.7×10~8CFU的SE对20只30日龄的SPF鸡进行攻毒，攻毒后5日内死亡的鸡定为感病组，存活了15日的鸡定为抗病组，两组鸡各6只，比较攻毒后0h、8h、16h、24h、3d、12d的载菌量及基因表达的差异。结果表明：（1）16h感病组血液中肠炎沙门氏菌的载菌量为1.1×107CFU，显著高于抗病组（P <0.05）。（2）16h抗病组鸡的体温42.6℃显著高于攻毒前0h的体温41.9℃（P <0.05），而感病鸡体温的增加没有达到显著（P>0.05）；3d时感病鸡的体温41.1℃显著低于抗病鸡的体温42.3℃（P <0.05）。（3）感病组鸡体重自16h持续下降，而抗病组16h后体重增加；在3d时感病组体重212.7g显著低于抗病组体重252.9g（P <0.05）。（4）感病鸡白细胞中TLR4、TLR2-1和TLR21的表达量显著低于抗病组（P <0.05）。（5）IFN-β和促炎症因子IL-6的基因表达量在抗病鸡中显著高于感病组（P<0.05）。（6）负调控基因ZNF493和TOLLIP仅在感病鸡中显著上调表达（P <0.05）。以上结果表明：TLRs基因的表达受到抑制导致炎症因子表达不足、载菌量增加、体重下降是感病组鸡死亡的主要原因。
试验三：表观遗传修饰对TLRs基因的表达调控。为深入研究感病鸡中SE感染后16h时TLRs的表达抑制是否与ZNF493依赖的表观调控相关，在细胞水平研究了甲基化酶和去乙酰化酶抑制剂对鸡单个核细胞TLRs的表达变化；并用重亚硫酸盐修饰后测序PCR（BSP）方法比较了感病组和抗病组鸡中TLR4、TLR21和TLR2-1基因启动子区域以及外显子区域的CpG岛的甲基化水平。结果表明：（1）在沙门氏菌感染的外周血单个核细胞中，甲基化酶抑制剂5-Aza-dc处理均可以显著增加TLR4的表达（P <0.05），5-Aza-dc和TrichostatinA都可以显著上调TLR21和TLR2-1的表达（P <0.05），但两者没有协同效应。（2）感病组鸡TLR4和TLR21启动子区域、TLR2-1的外显子CpG岛区域的甲基化程度显著高于抗病鸡（P <0.05）。结果表明：TLR4、TLR21和TLR2-1的表达受甲基化调控，感病鸡中TLR4、TLR21和TLR2-1的表达抑制可能由于过高的甲基化引起。
总体而言，本研究结果表明TLRs家族中TLR4、TLR21和TLR2-1是肠炎沙门氏菌感染的重要识别受体，鸡白细胞中TLR4、TLR21和TLR2-1的表达被抑制是导致沙门氏菌易感性增加、鸡死亡的主要原因，而ZNF493相关的表观修饰促使TLRs表达被抑制。
Toll-like receptors (TLRs) signaling pathways are the first lines in defense against Salmonellainfection. Ordinarily, TLRs signaling is activated immediately when chickens infected with Salmonella,but the molecular mechanism underlying susceptibility to S. enteritidis infection in chickens remainsunclear. This research included three sections:
Section1: The transcriptional regulation of TLRs in peripheral blood mononuclear cells (PBMCs) ofchickens infected in vitro with LPS or Salmonella. PBMCs were segregated from20specific-pathogen-free (SPF) chickens with30d old. Three treatments including LPS treatment,Salmonella enteritidis (S. enteritidis) infection and control groups were designed. The expression of9TLRs at1h,6h and24h post infection in PBMCs were investigated. In order to verify the effect of S.enteritidis infection dose on the expression of TLR4, TLR2-1and TLR21, PBMCs infected with S.enteritidis with1×10~9to1×10~4CFU with10folds dilution for6h. The results are as follow:(1)Expression of9TLRs including TLR4, TLR2-1and TLR21in PBMCs were upregulated by LPS orSalmonella.(2) At6h, expression of TLR4and TLR2were significantly upregulated in LPS treatmentgroup (P <0.05), but expression of TLR4was significantly downregulated compared with that ofcontrol (P <0.05), there was not significant change of expression of TLR21and TLR2(P>0.05). At24h, the upregulation of TLR21and TLR1-2was greater in Salmonella-treated group while thetranscription of TLR4, TLR1-1, TLR2(TLR2-1and TLR2-2) increased more significantly in LPS group(P <0.05).(4) The expression of TLR4, TLR21and TLR2-1decreased with different concentration ofSalmonella treatment. The depression of TLRs enhanced with the increase of concentration in the caseof low concentration (0～1×10~6CFU/mL) of Salmonella but go to the opposite direction in highconcentration (1×10~6～1×10~9CFU/mL).
Section2: The effect of transcriptional regulation of TLRs, pro-inflammatory genes and negativeregulators of TLRs on the susceptibility to Salmonella in Chickens. This section aimed to demonstratethe molecular mechanism underlying susceptibility to S. enteritidis infection. SPF chickens injectedwith8.7×108CFU of S. enteritidis were partitioned into two groups, one consisted of those fromSalmonella-susceptible chickens (died within5d after injection, n=6), the other consisted of sixSalmonella-resistant chickens that survived for15d after injection. The results showed that:(1) Thepresent study showed that the bacterial load1.1×10~7CFU in susceptible chickens was significantlyhigher than that in resistant chickens at16h post infection (P <0.05).(2) Temperature of resistantchickens with42.6℃at16h was significantly higher than41.9℃at0h (P <0.05), but the increase oftemperature in susceptible chickens was not significant (P>0.05); The temperature of susceptiblechickens with41.1℃on3d was significantly lower than that of resistant chickens with42.3℃(P <0.05). Body weight of susceptible chickens decreased after16h but that of resistant chickens increased;Body weight of susceptible chickens with212.7g was significantly lower than that of resistant chickenswith252.9g (P <0.05).(4) Expression of TLR4, TLR2-1and TLR21was strongly diminished in theleukocytes of susceptible chickens compared with those of resistant chickens (P <0.05).(5) The induction of expression of IFN-β and pro-inflammatory cytokine genes like IL-6, was greatly enhancedin the resistant chickens but not in susceptible chickens (P <0.05).(6) Contrasting with the reducedexpression of TLRs genes, which of the zinc finger protein493(ZNF493) gene and Toll-interactingprotein (TOLLIP) gene were enhanced in the susceptible chickens.
Section3: The role of epigenetic regulation in the depressed transcription of TLRs in susceptiblechickens. The main task of this section was to confirm whether ZNF493-related epigenetic modificationaccounted for the diminished expression of TLRs in susceptible chickens. The results demonstrated that:(1) The expression of TLR4in peripheral blood mononuclear cells (PBMCs) infected in vitro with S.enteritidis increased significantly as a result of treatment with5-Aza-2-deoxycytidine (5-Aza-dc) ortrichostatin A (TSA) while either5-Aza-dc or TSA was effective in up-regulating the expression ofTLR21and TLR2-1.(2) DNA methylation, in the predicted promoter and proximal promoter region ofTLR4and TLR21genes, and an exonic CpG island of the TLR2-1gene was significantly higher in thesusceptible chickens than that in resistant chickens. Taken together, the results demonstrate thatZNF493-related epigenetic modification in leukocytes probably accounts for increased susceptibility toS. enteritidis in chickens by diminishing the expression and response of TLR4, TLR21and TLR2-1.
引文
1.金伯泉，NLR:固有免疫模式识别受体中的一个重要家族．现代免疫学2006,26(3):177-182
2.李鹏，鸡白痢沙门氏菌致病性及MyD88-依赖途径信号分子表达的研究．[李鹏硕士学位论文]．郑州：河南农业大学，2009
3.强文军，王莹，路茜，王忠，β-1,3-葡聚糖对肠炎沙门氏菌感染鸡肠道氧化还原状态的影响．中国畜牧杂志2010,46(23):51-55
4.宋畅，TLR2,4基因SNP分析及TLR4基因3'非编码区SNP功能研究．[宋畅博士学位论文]．广州：中山大学，2006
5.宋咏梅，鸡TLR4信号通路与肠炎沙门氏菌感染关系的研究．[宋咏梅硕士学位论文]．北京：中国农业科学院，2010
6.孙冰，韩代书，Toll样受体信号通路的负调控．Progress in Biochemistry and Biophysics2009,36(12):1516-1522
7.汪进良，焦顺昌，胡毅和李瑾昱，重组人p53腺病毒联合顺铂对肺腺癌A549细胞基因表达的影响．中国医学科学院学报2010,32(4):383-387
8.汪敏，肠炎沙门氏菌实验性感染雏鸡的研究．[汪敏硕士学位论文]．重庆：西南大学，2009
9.王丹丹，固有免疫系统在铜绿假单胞菌肺部感染中的作用．[王丹丹博士学位论文]．北京：中国协和医科大学、中国医学科学院，2007
10.王秋生，一例乌骨鸡鸡白痢沙门氏菌感染的诊治．畜禽业2007,4:32-33
11.王晓铄，俞英，表观遗传对炎症的调控机制及其在奶牛乳房炎抗病育种中的应用前景．HEREDITAS (Beijing)2010,32(7):663-669
12.吴正蓉，Cripto-1(CR-1)在鼻咽癌中的作用及其机制研究．[吴正蓉博士学位论文]．广州：南方医科大学，2009
13.肖宇宏，白云，TOLL样受体：先天性免疫和获得性免疫的桥梁．局解手术学杂志2005,14(1):54-55
14.徐宁，于振海，王志强，曲洪林，孙毅，刘蛟，Toll样受体4及其负性调控因子tollip在结肠炎大鼠肠黏膜中的表达．第二军医大学学报2012,33(1):32-37
15.许金俊，王韵，陶建平，育成鸡鸡白痢沙门氏菌病的诊断和防治．中国兽医杂志2007,43(2):31-32
16.张朝正，鳜TLR9信号通路相关基因克隆和功能初步研究．[张朝正博士学位论文]．广州：中山大学，2009
17.赵保胜，桂枝汤等解表/清热方和相关成分对TLRs及其信号转导通路的影响．[赵保胜博士学位论文]．北京：中国中医科学院，2007
18.赵德明，王彩虹，鸡肠炎沙门氏菌感染症．中国兽医杂志1998,24(8):52-53
19. Abasht B., Kaiser M. G. and Lamont S. J., Toll-like receptor gene expression in cecum and spleenof advanced intercross line chicks infected with Salmonella enterica serovar Enteritidis. VetImmunol Immunopathol2008,123(3-4):314-323
20. Abreu M. T., Vora P., Faure E., Thomas L. S., Arnold E. T. and Arditi M., Decreased expression oftoll-like receptor-4and MD-2correlates with intestinal epithelial cell protection againstdysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. Journalof Immunology2001,167(3):1609-1616
21. Akira S. and Takeda K., Toll-like receptor signalling. Nat Rev Immunol2004,4(7):499-511
22. Alexander W. S., Suppressors of cytokine signalling (SOCS) in the immune system. Nat RevImmunol2002,2(6):410-416
23. An H., Xu H., Yu Y., Zhang M., Qi R., Yan X., Liu S., Wang W., Guo Z., Qin Z. and Cao X.,Up-regulation of TLR9gene expression by LPS in mouse macrophages via activation ofNF-kappaB, ERK and p38MAPK signal pathways. Immunol Lett2002a,81(3):165-169
24. An H., Yu Y., Zhang M., Xu H., Qi R., Yan X., Liu S., Wang W., Guo Z., Guo J., Qin Z. and Cao X.,Involvement of ERK, p38and NF-kappaB signal transduction in regulation of TLR2, TLR4andTLR9gene expression induced by lipopolysaccharide in mouse dendritic cells. Immunology2002b,106(1):38-45
25. Arbour N. C., Lorenz E., Schutte B. C., Zabner J., Kline J. N., Jones M., Frees K., Watt J. L. andSchwartz D. A., TLR4mutations are associated with endotoxin hyporesponsiveness in humans.Nature Genetics2000,25(2):187-+
26. Arpaia N., Godec J., Lau L., Sivick K. E., McLaughlin L. M., Jones M. B., Dracheva T., Peterson S.N., Monack D. M. and Barton G. M., TLR Signaling Is Required for Salmonella typhimuriumVirulence. Cell2011,144(5):675-688
27. Ayyanathan K., Lechner M. S., Bell P., Maul G. G., Schultz D. C., Yamada Y., Tanaka K., TorigoeK. and Rauscher F. J.,3rd, Regulated recruitment of HP1to a euchromatic gene induces mitoticallyheritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation. GenesDev2003,17(15):1855-1869
28. Babu S., Blauvelt C. P., Kumaraswami V. and Nutman T. B., Cutting edge: Diminished T cell TLRexpression and function modulates the immune response in human filarial infection. Journal ofImmunology2006,176(7):3885-3889
29. Barrow P. A., Lovell M. A. and Berchieri A., Immunisation of laying hens against Salmonellaenteritidis with live attenuated vaccines. Vet Rec1990,126(10):241-242
30. Beaumont C., Protais J., Pitel F., Leveque G., Malo D., Lantier F., Plisson-Petit F., Colin P., ProtaisM., Le Roy P., Elsen J. M., Milan D., Lantier I., Neau A., Salvat G. and Vignal A., Effect of twocandidate genes on the Salmonella carrier state in fowl. Poultry Science2003,82(5):721-726
31. Brownlie R., Zhu J. Z., Allan B., Mutwiri G. K., Babiuk L. A., Potter A. and Griebel P., ChickenTLR21acts as a functional homologue to mammalian TLR9in the recognition of CpGoligodeoxynucleotides. Molecular Immunology2009,46(15):3163-3170
32. Bulut Y., Faure E., Thomas L., Equils O. and Arditi M., Cooperation of toll-like receptor2and6for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface proteinA lipoprotein: Role of Toll-interacting protein and IL-1receptor signaling molecules in Toll-likereceptor2signaling. Journal of Immunology2001,167(2):987-994
33. Burns K., Clatworthy J., Martin L., Martinon F., Plumpton C., Maschera B., Lewis A., Ray K.,Tschopp J. and Volpe F., Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1receptor. Nature Cell Biology2000,2(6):346-351
34. Chahwan R., Wontakal S. N. and Roa S., Crosstalk between genetic and epigenetic informationthrough cytosine deamination. Trends in Genetics2010,26(10):443-448
35. Chahwan R., Wontakal S. N. and Roa S., The multidimensional nature of epigenetic informationand its role in disease. Discov Med2011,11(58):233-243
36. Chan C. W., Crafton E., Fan H. N., Flook J., Yoshimura K., Skarica M., Brockstedt D., Dubensky T.W., Stins M. F. and Lanier L. L., Interferon-producing killer dendritic cells provide a link betweeninnate and adaptive immunity. Nature medicine2006,12(2):207-213
37. Collier-Hyams L. S., Zeng H., Sun J., Tomlinson A. D., Bao Z. Q., Chen H., Madara J. L., Orth K.and Neish A. S., Cutting edge: Salmonella AvrA effector inhibits the key proinflammatory,anti-apoptotic NF-kappa B pathway. J Immunol2002,169(6):2846-2850
38. Comis, Seeing Salmonella move through pigs. Journal of Environmental Health2004,66(9):30-30
39. Cook D. N., Pisetsky D. S. and Schwartz D. A., Toll-like receptors in the pathogenesis of humandisease. Nat Immunol2004,5(10):975-979
40. Darton T., Guiver M., Naylor S., Jack D. L., Kaczmarski E. B., Borrow R. and Read R. C., Severityof meningococcal disease associated with genomic bacterial load. Clin Infect Dis2009,48(5):587-594
41. Deng C., Radu C., Diab A., Tsen M. F., Hussain R., Cowdery J. S., Racke M. K. and Thomas J. A.,IL-1receptor-associated kinase1regulates susceptibility to organ-specific autoimmunity. Journalof Immunology2003,170(6):2833-2842
42. Deng S. X., Cheng A. C., Wang M. S. and Cao P., Serovar-specific real-time quantitative detectionof Salmonella enteritidis in the gastrointestinal tract of ducks after oral challenge. Avian Dis2008,52(1):88-93
43. Durand V., Wong S. Y. C., Tough D. F. and Le Bon A., Shaping of adaptive immune responses tosoluble proteins by TLR agonists: A role for IFN-α/&bgr. Immunology and cell biology2004,82(6):596-602
44. Ehrlich M., Sanchez C., Shao C., Nishiyama R., Kehrl J., Kuick R., Kubota T. and Hanash S. M.,ICF, an immunodeficiency syndrome: DNA methyltransferase3B involvement, chromosomeanomalies, and gene dysregulation. Autoimmunity2008,41(4):253-271
45. Falls J. G., Pulford D. J., Wylie A. A. and Jirtle R. L., Genomic imprinting: Implications for humandisease. American Journal of Pathology1999,154(3):635-647
46. Feinberg A. P. and Vogelstein B., Hypomethylation distinguishes genes of some human cancersfrom their normal counterparts.1983a,
47. Feinberg A. P. and Vogelstein B., Hypomethylation of ras oncogenes in primary human cancers.Biochem Biophys Res Commun1983b,111(1):47-54
48. Fitzgerald K. A. and Chen Z. J., Sorting out Toll signals. Cell2006,125(5):834-836
49. Fukao T., Tanabe M., Terauchi Y., Ota T., Matsuda S., Asano T., Kadowaki T., Takeuchi T. andKoyasu S., PI3K-mediated negative feedback regulation of IL-12production in DCs. Natureimmunology2002,3(9):875-881
50. Fukui A., Inoue N., Matsumoto M., Nomura M., Yamada K., Matsuda Y., Toyoshima K. and SeyaT., Molecular cloning and functional characterization of chicken toll-like receptors. A singlechicken toll covers multiple molecular patterns. Journal of Biological Chemistry2001,276(50):47143-47149
51. Gaur U. and Aggarwal B. B., Regulation of proliferation, survival and apoptosis by members of theTNF superfamily. Biochem Pharmacol2003,66(8):1403-1408
52. Gonzalez-Zulueta M., Bender C. M., Yang A. S., Nguyen T., Beart R. W., Van Tornout J. M. andJones P. A., Methylation of the5' CpG island of the p16/CDKN2tumor suppressor gene in normaland transformed human tissues correlates with gene silencing. Cancer Res1995,55(20):4531-4535
53. Halford S., Mattei M. G., Daw S. and Scambler P. J., A novel C2H2zinc-finger protein gene(ZNF160) maps to human chromosome19q13.3-q13.4. Genomics1995,25(1):322-323
54. Haraga A., Ohlson M. B. and Miller S. I., Salmonellae interplay with host cells. Nat Rev Microbiol2008,6(1):53-66
55. Hausmann M., Kiessling S., Mestermann S., Webb G., Sp ttl T., Andus T., Sch lmerich J., HerfarthH., Ray K. and Falk W., Toll-like receptors2and4are up-regulated during intestinal inflammation.Gastroenterology2002,122(7):1987-2000
56. Herman J. G., Civin C. I., Issa J. P., Collector M. I., Sharkis S. J. and Baylin S. B., Distinct patternsof inactivation of p15INK4B and p16INK4A characterize the major types of hematologicalmalignancies. Cancer Res1997,57(5):837-841
57. Higuchi M., Matsuo A., Shingai M., Shida K., Ishii A., Funami K., Suzuki Y., Oshiumi H.,Matsumoto M. and Seya T., Combinational recognition of bacterial lipoproteins and peptidoglycanby chicken Toll-like receptor2subfamily. Dev Comp Immunol2008,32(2):147-155
58. Hisano M., Ohta H., Nishimune Y. and Nozaki M., Methylation of CpG dinucleotides in the openreading frame of a testicular germ cell-specific intronless gene, Tact1/Actl7b, represses itsexpression in somatic cells. Nucleic Acids Res2003,31(16):4797-4804
59. Hu J. X., Bumstead N., Barrow P., Sebastiani G., Olien L., Morgan K. and Malo D., Resistance tosalmonellosis in the chicken is linked to NRAMP1and TNC. Genome Research1997,7(7):693-704
60. Hubert F. X., Voisine C., Louvet C., Heslan J. M., Ouabed A., Heslan M. and Josien R.,Differential pattern recognition receptor expression but stereotyped responsiveness in rat spleendendritic cell subsets. The Journal of Immunology2006,177(2):1007-1016
61. Iqbal M., Philbin V. J., Withanage G. S. K., Wigley P., Beal R. K., Goodchild M. J., Barrow P.,McConnell I., Maskell D. J., Young J., Bumstead N., Boyd Y. and Smith A. L., Identification andfunctional characterization of chicken Toll-like receptor5reveals a fundamental role in the biologyof infection with Salmonella enterica serovar typhimurium. Infection and immunity2005,73(4):2344-2350
62. Isaacs A. and Lindenmann J., Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci1957,147(927):258-267
63. Jakobsson J., Cordero M. I., Bisaz R., Groner A. C., Busskamp V., Bensadoun J. C., Cammas F.,Losson R., Mansuy I. M., Sandi C. and Trono D., KAP1-mediated epigenetic repression in theforebrain modulates behavioral vulnerability to stress. Neuron2008,60(5):818-831
64. Jirtle R. L., Genomic imprinting and cancer. Experimental Cell Research1999,248(1):18-24
65. Kabelitz D., Expression and function of Toll-like receptors in T lymphocytes. Curr Opin Immunol2007,19(1):39-45
66. Katso R., Okkenhaug K., Ahmadi K., White S., Timms J. and Waterfield M. D., Cellular functionof phosphoinositide3-kinases: Implications for development, immunity, homeostasis, and cancer.Annual Review of Cell and Developmental Biology2001,17(615-675
67. Kawai T. and Akira S., TLR signaling. Seminars in Immunology2007,19(1):24-32
68. Keestra A. M., de Zoete M. R., van Aubel R. A. and van Putten J. P., The central leucine-rich repeatregion of chicken TLR16dictates unique ligand specificity and species-specific interaction withTLR2. J Immunol2007,178(11):7110-7119
69. Kenny E. F. and O'Neill L. A. J., Signalling adaptors used by Toll-like receptors: An update.Cytokine2008,43(3):342-349
70. Kinjyo I., Hanada T., Inagaki-Ohara K., Mori H., Aki D., Ohishi M., Yoshida H., Kubo M. andYoshimura A., SOCS1/JAB is a negative regulator of LPS-induced macrophage activation.Immunity2002,17(5):583-591
71. Kogut M. H., Swaggerty C., He H. Q., Pevzner I. and Kaiser P., Toll-like receptor agonistsstimulate differential functional activation and cytokine and chemokine gene expression inheterophils isolated from chickens with differential innate responses. Microbes and Infection2006,8(7):1866-1874
72. Kondo T., Bobek M. P., Kuick R., Lamb B., Zhu X. X., Narayan A., Bourc'his D.,Viegas-Pequignot E., Ehrlich M. and Hanash S. M., Whole-genome methylation scan in ICFsyndrome: hypomethylation of non-satellite DNA repeats D4Z4and NBL2. Human MolecularGenetics2000,9(4):597-604
73. Kornberg R. D. and Lorch Y. L., Twenty-five years of the nucleosome, fundamental particle of theeukaryote chromosome. Cell1999,98(3):285-294
74. Kuroishi T., Tanaka Y., Sakai A., Sugawara Y., Komine K. I. and Sugawara S., Human parotidsaliva contains soluble toll-like receptor (TLR)2and modulates TLR2-mediated interleukin-8production by monocytic cells. Molecular Immunology2007,44(8):1969-1976
75. Lazarevic V., Nolt D. and Flynn J. A. L., Long-term control of Mycobacterium tuberculosisinfection is mediated by dynamic immune responses. Journal of Immunology2005,175(2):1107-1117
76. Leveque G., Forgetta V., Morroll S., Smith A. L., Bumstead N., Barrow P., Loredo-Osti J., MorganK. and Malo D., Allelic variation in TLR4is linked to susceptibility to Salmonella enterica serovarTyphimurium infection in chickens. Infection and immunity2003a,71(3):1116-1124
77. Leveque G., Forgetta V., Morroll S., Smith A. L., Bumstead N., Barrow P., Loredo-Osti J. C.,Morgan K. and Malo D., Allelic variation in TLR4is linked to susceptibility to Salmonella entericaserovar Typhimurium infection in chickens. Infect Immun2003b,71(3):1116-1124
78. Li P., Xia P., Wen J., Zheng M., Chen J., Zhao J., Jiang R., Liu R. and Zhao G., Up-regulation ofthe MyD88-dependent pathway of TLR signaling in spleen and caecum of young chickens infectedwith Salmonella serovar Pullorum. Vet Microbiol2010,143(2-4):346-351
79. Liew F. Y., Xu D., Brint E. K. and O'Neill L. A., Negative regulation of toll-like receptor-mediatedimmune responses. Nat Rev Immunol2005a,5(6):446-458
80. Liew F. Y., Xu D. M., Brint E. K. and O'Neill L. A. J., Negative regulation of Toll-likereceptor-mediated immune responses. Nature Reviews Immunology2005b,5(6):446-458
81. Lindell K. A., Saeed A. M. and McCabe G. P., Evaluation of resistance of four strains ofcommercial laying hens to experimental infection with Salmonella enteritidis phage type eight.Poult Sci1994,73(6):757-762
82. Liu P. T., Stenger S., Li H. Y., Wenzel L., Tan B. H., Krutzik S. R., Ochoa M. T., Schauber J., WuK., Meinken C., Kamen D. L., Wagner M., Bals R., Steinmeyer A., Zugel U., Gallo R. L.,Eisenberg D., Hewison M., Hollis B. W., Adams J. S., Bloom B. R. and Modlin R. L., Toll-likereceptor triggering of a vitamin D-mediated human antimicrobial response. Science2006,311(5768):1770-1773
83. Liu Y., Wang Y., Yamakuchi M., Isowaki S., Nagata E., Kanmura Y., Kitajima I. and Maruyama I.,Upregulation of toll-like receptor2gene expression in macrophage response to peptidoglycan andhigh concentration of lipopolysaccharide is involved in NF-κB activation. Infection and immunity2001,69(5):2788-2796
84. Lo P. K. and Sukumar S., Epigenomics and breast cancer. Pharmacogenomics2008,9(12):1879-1902
85. Lorenz E., Mira J. P., Frees K. L. and Schwartz D. A., Relevance of mutations in the TLR4receptor in patients with gram-negative septic shock. Arch Intern Med2002,162(9):1028-1032
86. MacLeod H. and Wetzler L. M., T cell activation by TLRs: a role for TLRs in the adaptive immuneresponse. Sci STKE2007,2007(402): pe48
87. Mansell A., Smith R., Doyle S. L., Gray P., Fenner J. E., Crack P. J., Nicholson S. E., Hilton D. J.,O'Neill L. A. J. and Hertzog P. J., Suppressor of cytokine signaling1negatively regulates Toll-likereceptor signaling by mediating Mal degradation. Nature immunology2006,7(2):148-155
88. Maris N. A., Dessing M. C., de Vos A. F., Bresser P., van der Zee J. S., Jansen H. M., Spek C. A.and van der Poll T., Toll-like receptor mRNA levels in alveolar macrophages after inhalation ofendotoxin. Eur Respir J2006,28(3):622-626
89. Martin-Subero J. I. and Esteller M., Profiling Epigenetic Alterations in Disease. EpigeneticContributions in Autoimmune Disease2011,711(162-177
90. Martin M. U. and Wesche H., Summary and comparison of the signaling mechanisms of theToll/interleukin-1receptor family. Biochim Biophys Acta2002,1592(3):265-280
91. Matarazzo M. R., Boyle S., D'Esposito M. and Bickmore W. A., Chromosome territoryreorganization in a human disease with altered DNA methylation. Proceedings of the NationalAcademy of Sciences of the United States of America2007,104(42):16546-16551
92. McLoughlin M., Mcllroy S. and Neill S., A major outbreak of botulism in cattle being fed ensiledpoultry litter. Veterinary Record1988,122(24):579-581
93. Medzhitov R. and Janeway C. A., Innate immunity: The virtues of a nonclonal system ofrecognition. Cell1997,91(3):295-298
94. Melmed G., Thomas L. S., Lee N., Tesfay S. Y., Lukasek K., Michelsen K. S., Zhou Y. H., Hu B.,Arditi M. and Abreu M. T., Human intestinal epithelial cells are broadly unresponsive to toll-likereceptor2-dependent bacterial ligands: Implications for host-microbial interactions in the gut.Journal of Immunology2003,170(3):1406-1415
95. Monack D. M., Mueller A. and Falkow S., Persistent bacterial infections: the interface of thepathogen and the host immune system. Nat Rev Microbiol2004,2(9):747-765
96. Morison I. M. and Reeve A. E., A catalogue of imprinted genes and parent-of-origin effects inhumans and animals. Human Molecular Genetics1998,7(10):1599-1609
97. Nadkarni M. A., Martin F. E., Jacques N. A. and Hunter N., Determination of bacterial load byreal-time PCR using a broad-range (universal) probe and primers set. Microbiology2002,148(Pt1):257-266
98. Naiki Y., Michelsen K. S., Schroder N. W. J., Alsabeh R., Slepenkin A., Zhang W. X., Chen S., WeiB., Bulut Y., Wong M. H., Peterson E. M. and Arditi M., MyD88is pivotal for the earlyinflammatory response and subsequent bacterial clearance and survival in a mouse model ofChlamydia pneumoniae pneumonia. Journal of Biological Chemistry2005a,280(32):29242-29249
99. Naiki Y., Michelsen K. S., Zhang W., Chen S., Doherty T. M. and Arditi M., Transforming growthfactor-beta differentially inhibits MyD88-dependent, but not TRAM-and TRIF-dependent,lipopolysaccharide-induced TLR4signaling. J Biol Chem2005b,280(7):5491-5495
100. Naka T., Matsumoto T., Narazaki M., Fujimoto M., Morita Y., Ohsawa Y., Saito H., Nagasawa T.,Uchiyama Y. and Kishimoto T., Accelerated apoptosis of lymphocytes by augmented induction ofBax in SSI-1(STAT-induced STAT inhibitor-1) deficient mice. Proc Natl Acad Sci U S A1998,95(26):15577-15582
101. Nakagawa R., Naka T., Tsutsui H., Fujimoto M., Kimura A., Abe T., Seki E., Sato S., Takeuchi O.and Takeda K., SOCS-1participates in negative regulation of LPS responses. Immunity2002a,17(5):677-687
102. Nakagawa R., Naka T., Tsutsui H., Fujimoto M., Kimura A., Abe T., Seki E., Sato S., Takeuchi O.,Takeda K., Akira S., Yamanishi K., Kawase I., Nakanishi K. and Kishimoto T., SOCS-1participates in negative regulation of LPS responses. Immunity2002b,17(5):677-687
103. Nakayama M., Wada M., Harada T., Nagayama J., Kusaba H., Ohshima K., Kozuru M., KomatsuH., Ueda R. and Kuwano M., Hypomethylation status of CpG sites at the promoter region andoverexpression of the human MDR1gene in acute myeloid leukemias. Blood1998,92(11):4296-4307
104. Nerren J. R., He H. Q., Genovese K. and Kogut M. H., Expression of the avian-specific toll-likereceptor15in chicken heterophils is mediated by Gram-negative and Gram-positive bacteria, butnot TLR agonists. Veterinary Immunology and Immunopathology2010,136(1-2):151-156
105. Nguyen T. H., Mai N. L., Le T. P., Ha V., Nguyen T. C., Tran T. H., Farrar J. J. and Dunstan S. J.,Toll-like receptor4(TLR4) and typhoid fever in Vietnam. PLoS One2009,4(3): e4800
106. Palmer B. R. and Marinus M. G., The dam and dcm strains of Escherichia coli--a review. Gene1994,143(1):1-12
107. Philbin V. J., Iqbal M., Boyd Y., Goodchild M. J., Beal R. K., Bumstead N., Young J. and Smith A.L., Identification and characterization of a functional, alternatively spliced Toll-like receptor7(TLR7) and genomic disruption of TLR8in chickens. Immunology2005,114(4):507-521
108. Poltorak A., He X., Smirnova I., Liu M. Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M.,Galanos C., Freudenberg M., Ricciardi-Castagnoli P., Layton B. and Beutler B., Defective LPSsignaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4gene. Science1998,282(5396):2085-2088
109. Pothlichet J., Chignard M. and Si-Tahar M., Cutting edge: innate immune response triggered byinfluenza A virus is negatively regulated by SOCS1and SOCS3through aRIG-I/IFNAR1-dependent pathway. J Immunol2008a,180(4):2034-2038
110. Pothlichet J., Chignard M. and Si-Tahar M., Innate immune response triggered by influenza a virusis negatively regulated by SOCS1and SOCS3through a RIG-I/IFNARI-dependent pathway.Journal of Immunology2008b,180(4):2034-2038
111. Re F. and Strominger J. L., IL-10released by concomitant TLR2stimulation blocks the inductionof a subset of Th1cytokines that are specifically induced by TLR4or TLR3in human dendriticcells. J Immunol2004,173(12):7548-7555
112. Renn C. N., Sanchez D. J., Ochoa M. T., Legaspi A. J., Oh C. K., Liu P. T., Krutzik S. R., Sieling P.A., Cheng G. and Modlin R. L., TLR activation of Langerhans cell-like dendritic cells triggers anantiviral immune response. The Journal of Immunology2006,177(1):298-305
113. Ruprecht C. R. and Lanzavecchia A., Toll‐like receptor stimulation as a third signal required foractivation of human naive B cells. European journal of immunology2006,36(4):810-816
114. Sadeyen J. R., Trotereau J., Protais J., Beaumont C., Sellier N., Salvat G., Velge P. and LalmanachA. C., Salmonella carrier-state in hens: study of host resistance by a gene expression approach.Microbes and Infection2006,8(5):1308-1314
115. Schwarz H., Schneider K., Ohnemus A., Lavric M., Kothlow S., Bauer S., Kaspers B. and StaeheliP., Chicken toll-like receptor3recognizes its cognate ligand when ectopically expressed in humancells. J Interferon Cytokine Res2007,27(2):97-101
116. Shilatifard A., Chromatin modifications by methylation and ubiquitination: Implications in theregulation of gene expression. Annual Review of Biochemistry2006,75(243-269
117. Shuto T., Furuta T., Oba M., Xu H. D., Li J. D., Cheung J., Gruenert D. C., Uehara A., Suico M. A.,Okiyoneda T. and Kai H., Promoter hypomethylation of Toll-like receptor-2gene is associated withincreased proinflammatory response toward bacterial peptidoglycan in cystic fibrosis bronchialepithelial cells. Faseb Journal2006,20(2):782-+
118. Smith-Vaughan H., Byun R., Nadkarni M., Jacques N. A., Hunter N., Halpin S., Morris P. S. andLeach A. J., Measuring nasal bacterial load and its association with otitis media. BMC Ear NoseThroat Disord2006,6(10
119. Sripathy S. P., Stevens J. and Schultz D. C., The KAP1corepressor functions to coordinate theassembly of de novo HP1-demarcated microenvironments of heterochromatin required for KRABzinc finger protein-mediated transcriptional repression. Mol Cell Biol2006,26(22):8623-8638
120. Starr R., Metcalf D., Elefanty A. G., Brysha M., Willson T. A., Nicola N. A., Hilton D. J. andAlexander W. S., Liver degeneration and lymphoid deficiencies in mice lacking suppressor ofcytokine signaling-1. Proceedings of the National Academy of Sciences1998,95(24):14395
121. Sun S., Wang X., Wu X., Zhao Y., Wang F., Liu X., Song Y., Wu Z. and Liu M., Toll-like receptoractivation by helminths or helminth products to alleviate inflammatory bowel disease. ParasitVectors2011,4(186
122. Suter C. M., Martin D. I. and Ward R. L., Hypomethylation of L1retrotransposons in colorectalcancer and adjacent normal tissue. Int J Colorectal Dis2004,19(2):95-101
123. Suzuki N., Suzuki S., Duncan G. S., Millar D. G., Wada T., Mirtsos C., Takada H., Wakeham A.,Itie A. and Li S., Severe impairment of interleukin-1and Toll-like receptor signalling in micelacking IRAK-4. Nature2002,416(6882):750-756
124. Takahashi K., Sugi Y., Hosono A. and Kaminogawa S., Epigenetic regulation of TLR4geneexpression in intestinal epithelial cells for the maintenance of intestinal homeostasis. The Journalof Immunology2009a,183(10):6522-6529
125. Takahashi K., Sugi Y., Hosono A. and Kaminogawa S., Epigenetic Regulation of TLR4GeneExpression in Intestinal Epithelial Cells for the Maintenance of Intestinal Homeostasis. Journal ofImmunology2009b,183(10):6522-6529
126. Takeda K. and Akira S., Toll-like receptors in innate immunity. International immunology2005,17(1):1-14
127. Temperley N. D., Berlin S., Paton I. R., Griffin D. K. and Burt D. W., Evolution of the chickenToll-like receptor gene family: a story of gene gain and gene loss. BMC genomics2008,9(1):62
128. Thoma-Uszynski S., Stenger S., Takeuchi O., Ochoa M. T., Engele M., Sieling P. A., Barnes P. F.,Rollinghoff M., Bolcskei P. L., Wagner M., Akira S., Norgard M. V., Belisle J. T., Godowski P. J.,Bloom B. R. and Modlin R. L., Induction of direct antimicrobial activity through mammaliantoll-like receptors. Science2001,291(5508):1544-1547
129. Tycko B., Epigenetic gene silencing in cancer. J Clin Invest2000,105(4):401-407
130. Ulevitch R. J. and Tobias P. S., Receptor-dependent mechanisms of cell stimulation by bacterialendotoxin. Annu Rev Immunol1995,13(437-457
131. van Hemert S., Hoekman A. J., Smits M. A. and Rebel J. M., Immunological and gene expressionresponses to a Salmonella infection in the chicken intestine. Vet Res2007,38(1):51-63
132. van Oers N. S. and Chen Z. J., Cell biology. Kinasing and clipping down the NF-kappa B trail.Science2005,308(5718):65-66
133. Vanden Eijnden S., Goriely S., De Wit D., Goldman M. and Willems F., Preferential production ofthe IL‐12(p40)/IL‐23(p19) heterodimer by dendritic cells from human newborns. Europeanjournal of immunology2006,36(1):21-26
134. Vanden E. S., Goriely S., De Wit D., Goldman M. and Willems F., Preferential production of theIL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns. European journal ofimmunology2006,36(1):21
135. Vanselow J., Yang W., Herrmann J., Zerbe H., Schuberth H. J., Petzl W., Tomek W. and Seyfert H.M., DNA-remethylation around a STAT5-binding enhancer in the αS1-casein promoter isassociated with abrupt shutdown of αS1-casein synthesis during acute mastitis. Journal ofmolecular endocrinology2006,37(3):463-477
136. Vicente J., Higgins S., Bielke L., Tellez G., Donoghue D., Donoghue A. and Hargis B., Effect ofprobiotic culture candidates on Salmonella prevalence in commercial turkey houses. Journal ofApplied Poultry Research2007,16(3):471-476
137. Wang N., Strugnell R., Wijburg O. and Brodnicki T., Measuring Bacterial Load and ImmuneResponses in Mice Infected with Listeria monocytogenes. J Vis Exp2011,(54): e30761-8
138. Waterer G. and Rello J., Why should we measure bacterial load when treating community-acquiredpneumonia? Current Opinion in Infectious Diseases2011,24(2):137-141
139. Weighardt H., Kaiser-Moore S., Vabulas R. M., Kirschning C. J., Wagner H. and Holzmann B.,Cutting edge: myeloid differentiation factor88deficiency improves resistance against sepsiscaused by polymicrobial infection. The Journal of Immunology2002,169(6):2823-2827
140. Weiss D. S., Raupach B., Takeda K., Akira S. and Zychlinsky A., Toll-like receptors are temporallyinvolved in host defense. J Immunol2004,172(7):4463-4469
141. White D. G., Zhao S., Sudler R., Ayers S., Friedman S., Chen S., McDermott P. F., McDermott S.,Wagner D. D. and Meng J. H., The isolation of antibiotic-resistant Salmonella from retail groundmeats. New England Journal of Medicine2001,345(16):1147-1154
142. Wille-Reece U., Flynn B. J., Loré K., Koup R. A., Miles A. P., Saul A., Kedl R. M., Mattapallil J. J.,Weiss W. R. and Roederer M., Toll-like receptor agonists influence the magnitude and quality ofmemory T cell responses after prime-boost immunization in nonhuman primates. The Journal ofexperimental medicine2006,203(5):1249-1258
143. Wiznerowicz M., Jakobsson J., Szulc J., Liao S., Quazzola A., Beermann F., Aebischer P. andTrono D., The Kruppel-associated box repressor domain can trigger de Novo promoter methylationduring mouse early embryogenesis. Journal of Biological Chemistry2007,282(47):34535-34541
144. Yang H., Wei J., Zhang H., Lin L., Zhang W. and He S., Upregulation of Toll-like receptor (TLR)expression and release of cytokines from P815mast cells by GM-CSF. BMC Cell Biol2009,10(37
145. Yang H., Wei J., Zhang H., Song W., Wei W., Zhang L., Qian K. and He S., Upregulation ofToll-like Receptor (TLR) expression and release of cytokines from mast cells by IL-12. CellPhysiol Biochem2010,26(3):337-346
146. Yoshida H., Jono H., Kai H. and Li J. D., The tumor suppressor cylindromatosis (CYLD) acts as anegative regulator for toll-like receptor2signaling via negative cross-talk with TRAF6and TRAF7.Journal of Biological Chemistry2005,280(49):41111-41121
147. Zhang G. L. and Ghosh S., Negative regulation of toll-like receptor-mediated signaling by Tollip.Journal of Biological Chemistry2002,277(9):7059-706
2.李鹏，鸡白痢沙门氏菌致病性及MyD88-依赖途径信号分子表达的研究．[李鹏硕士学位论文]．郑州：河南农业大学，2009
3.强文军，王莹，路茜，王忠，β-1,3-葡聚糖对肠炎沙门氏菌感染鸡肠道氧化还原状态的影响．中国畜牧杂志2010,46(23):51-55
4.宋畅，TLR2,4基因SNP分析及TLR4基因3'非编码区SNP功能研究．[宋畅博士学位论文]．广州：中山大学，2006
5.宋咏梅，鸡TLR4信号通路与肠炎沙门氏菌感染关系的研究．[宋咏梅硕士学位论文]．北京：中国农业科学院，2010
6.孙冰，韩代书，Toll样受体信号通路的负调控．Progress in Biochemistry and Biophysics2009,36(12):1516-1522
7.汪进良，焦顺昌，胡毅和李瑾昱，重组人p53腺病毒联合顺铂对肺腺癌A549细胞基因表达的影响．中国医学科学院学报2010,32(4):383-387
8.汪敏，肠炎沙门氏菌实验性感染雏鸡的研究．[汪敏硕士学位论文]．重庆：西南大学，2009
9.王丹丹，固有免疫系统在铜绿假单胞菌肺部感染中的作用．[王丹丹博士学位论文]．北京：中国协和医科大学、中国医学科学院，2007
10.王秋生，一例乌骨鸡鸡白痢沙门氏菌感染的诊治．畜禽业2007,4:32-33
11.王晓铄，俞英，表观遗传对炎症的调控机制及其在奶牛乳房炎抗病育种中的应用前景．HEREDITAS (Beijing)2010,32(7):663-669
12.吴正蓉，Cripto-1(CR-1)在鼻咽癌中的作用及其机制研究．[吴正蓉博士学位论文]．广州：南方医科大学，2009
13.肖宇宏，白云，TOLL样受体：先天性免疫和获得性免疫的桥梁．局解手术学杂志2005,14(1):54-55
14.徐宁，于振海，王志强，曲洪林，孙毅，刘蛟，Toll样受体4及其负性调控因子tollip在结肠炎大鼠肠黏膜中的表达．第二军医大学学报2012,33(1):32-37
15.许金俊，王韵，陶建平，育成鸡鸡白痢沙门氏菌病的诊断和防治．中国兽医杂志2007,43(2):31-32
16.张朝正，鳜TLR9信号通路相关基因克隆和功能初步研究．[张朝正博士学位论文]．广州：中山大学，2009
17.赵保胜，桂枝汤等解表/清热方和相关成分对TLRs及其信号转导通路的影响．[赵保胜博士学位论文]．北京：中国中医科学院，2007
18.赵德明，王彩虹，鸡肠炎沙门氏菌感染症．中国兽医杂志1998,24(8):52-53
19. Abasht B., Kaiser M. G. and Lamont S. J., Toll-like receptor gene expression in cecum and spleenof advanced intercross line chicks infected with Salmonella enterica serovar Enteritidis. VetImmunol Immunopathol2008,123(3-4):314-323
20. Abreu M. T., Vora P., Faure E., Thomas L. S., Arnold E. T. and Arditi M., Decreased expression oftoll-like receptor-4and MD-2correlates with intestinal epithelial cell protection againstdysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. Journalof Immunology2001,167(3):1609-1616
21. Akira S. and Takeda K., Toll-like receptor signalling. Nat Rev Immunol2004,4(7):499-511
22. Alexander W. S., Suppressors of cytokine signalling (SOCS) in the immune system. Nat RevImmunol2002,2(6):410-416
23. An H., Xu H., Yu Y., Zhang M., Qi R., Yan X., Liu S., Wang W., Guo Z., Qin Z. and Cao X.,Up-regulation of TLR9gene expression by LPS in mouse macrophages via activation ofNF-kappaB, ERK and p38MAPK signal pathways. Immunol Lett2002a,81(3):165-169
24. An H., Yu Y., Zhang M., Xu H., Qi R., Yan X., Liu S., Wang W., Guo Z., Guo J., Qin Z. and Cao X.,Involvement of ERK, p38and NF-kappaB signal transduction in regulation of TLR2, TLR4andTLR9gene expression induced by lipopolysaccharide in mouse dendritic cells. Immunology2002b,106(1):38-45
25. Arbour N. C., Lorenz E., Schutte B. C., Zabner J., Kline J. N., Jones M., Frees K., Watt J. L. andSchwartz D. A., TLR4mutations are associated with endotoxin hyporesponsiveness in humans.Nature Genetics2000,25(2):187-+
26. Arpaia N., Godec J., Lau L., Sivick K. E., McLaughlin L. M., Jones M. B., Dracheva T., Peterson S.N., Monack D. M. and Barton G. M., TLR Signaling Is Required for Salmonella typhimuriumVirulence. Cell2011,144(5):675-688
27. Ayyanathan K., Lechner M. S., Bell P., Maul G. G., Schultz D. C., Yamada Y., Tanaka K., TorigoeK. and Rauscher F. J.,3rd, Regulated recruitment of HP1to a euchromatic gene induces mitoticallyheritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation. GenesDev2003,17(15):1855-1869
28. Babu S., Blauvelt C. P., Kumaraswami V. and Nutman T. B., Cutting edge: Diminished T cell TLRexpression and function modulates the immune response in human filarial infection. Journal ofImmunology2006,176(7):3885-3889
29. Barrow P. A., Lovell M. A. and Berchieri A., Immunisation of laying hens against Salmonellaenteritidis with live attenuated vaccines. Vet Rec1990,126(10):241-242
30. Beaumont C., Protais J., Pitel F., Leveque G., Malo D., Lantier F., Plisson-Petit F., Colin P., ProtaisM., Le Roy P., Elsen J. M., Milan D., Lantier I., Neau A., Salvat G. and Vignal A., Effect of twocandidate genes on the Salmonella carrier state in fowl. Poultry Science2003,82(5):721-726
31. Brownlie R., Zhu J. Z., Allan B., Mutwiri G. K., Babiuk L. A., Potter A. and Griebel P., ChickenTLR21acts as a functional homologue to mammalian TLR9in the recognition of CpGoligodeoxynucleotides. Molecular Immunology2009,46(15):3163-3170
32. Bulut Y., Faure E., Thomas L., Equils O. and Arditi M., Cooperation of toll-like receptor2and6for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface proteinA lipoprotein: Role of Toll-interacting protein and IL-1receptor signaling molecules in Toll-likereceptor2signaling. Journal of Immunology2001,167(2):987-994
33. Burns K., Clatworthy J., Martin L., Martinon F., Plumpton C., Maschera B., Lewis A., Ray K.,Tschopp J. and Volpe F., Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1receptor. Nature Cell Biology2000,2(6):346-351
34. Chahwan R., Wontakal S. N. and Roa S., Crosstalk between genetic and epigenetic informationthrough cytosine deamination. Trends in Genetics2010,26(10):443-448
35. Chahwan R., Wontakal S. N. and Roa S., The multidimensional nature of epigenetic informationand its role in disease. Discov Med2011,11(58):233-243
36. Chan C. W., Crafton E., Fan H. N., Flook J., Yoshimura K., Skarica M., Brockstedt D., Dubensky T.W., Stins M. F. and Lanier L. L., Interferon-producing killer dendritic cells provide a link betweeninnate and adaptive immunity. Nature medicine2006,12(2):207-213
37. Collier-Hyams L. S., Zeng H., Sun J., Tomlinson A. D., Bao Z. Q., Chen H., Madara J. L., Orth K.and Neish A. S., Cutting edge: Salmonella AvrA effector inhibits the key proinflammatory,anti-apoptotic NF-kappa B pathway. J Immunol2002,169(6):2846-2850
38. Comis, Seeing Salmonella move through pigs. Journal of Environmental Health2004,66(9):30-30
39. Cook D. N., Pisetsky D. S. and Schwartz D. A., Toll-like receptors in the pathogenesis of humandisease. Nat Immunol2004,5(10):975-979
40. Darton T., Guiver M., Naylor S., Jack D. L., Kaczmarski E. B., Borrow R. and Read R. C., Severityof meningococcal disease associated with genomic bacterial load. Clin Infect Dis2009,48(5):587-594
41. Deng C., Radu C., Diab A., Tsen M. F., Hussain R., Cowdery J. S., Racke M. K. and Thomas J. A.,IL-1receptor-associated kinase1regulates susceptibility to organ-specific autoimmunity. Journalof Immunology2003,170(6):2833-2842
42. Deng S. X., Cheng A. C., Wang M. S. and Cao P., Serovar-specific real-time quantitative detectionof Salmonella enteritidis in the gastrointestinal tract of ducks after oral challenge. Avian Dis2008,52(1):88-93
43. Durand V., Wong S. Y. C., Tough D. F. and Le Bon A., Shaping of adaptive immune responses tosoluble proteins by TLR agonists: A role for IFN-α/&bgr. Immunology and cell biology2004,82(6):596-602
44. Ehrlich M., Sanchez C., Shao C., Nishiyama R., Kehrl J., Kuick R., Kubota T. and Hanash S. M.,ICF, an immunodeficiency syndrome: DNA methyltransferase3B involvement, chromosomeanomalies, and gene dysregulation. Autoimmunity2008,41(4):253-271
45. Falls J. G., Pulford D. J., Wylie A. A. and Jirtle R. L., Genomic imprinting: Implications for humandisease. American Journal of Pathology1999,154(3):635-647
46. Feinberg A. P. and Vogelstein B., Hypomethylation distinguishes genes of some human cancersfrom their normal counterparts.1983a,
47. Feinberg A. P. and Vogelstein B., Hypomethylation of ras oncogenes in primary human cancers.Biochem Biophys Res Commun1983b,111(1):47-54
48. Fitzgerald K. A. and Chen Z. J., Sorting out Toll signals. Cell2006,125(5):834-836
49. Fukao T., Tanabe M., Terauchi Y., Ota T., Matsuda S., Asano T., Kadowaki T., Takeuchi T. andKoyasu S., PI3K-mediated negative feedback regulation of IL-12production in DCs. Natureimmunology2002,3(9):875-881
50. Fukui A., Inoue N., Matsumoto M., Nomura M., Yamada K., Matsuda Y., Toyoshima K. and SeyaT., Molecular cloning and functional characterization of chicken toll-like receptors. A singlechicken toll covers multiple molecular patterns. Journal of Biological Chemistry2001,276(50):47143-47149
51. Gaur U. and Aggarwal B. B., Regulation of proliferation, survival and apoptosis by members of theTNF superfamily. Biochem Pharmacol2003,66(8):1403-1408
52. Gonzalez-Zulueta M., Bender C. M., Yang A. S., Nguyen T., Beart R. W., Van Tornout J. M. andJones P. A., Methylation of the5' CpG island of the p16/CDKN2tumor suppressor gene in normaland transformed human tissues correlates with gene silencing. Cancer Res1995,55(20):4531-4535
53. Halford S., Mattei M. G., Daw S. and Scambler P. J., A novel C2H2zinc-finger protein gene(ZNF160) maps to human chromosome19q13.3-q13.4. Genomics1995,25(1):322-323
54. Haraga A., Ohlson M. B. and Miller S. I., Salmonellae interplay with host cells. Nat Rev Microbiol2008,6(1):53-66
55. Hausmann M., Kiessling S., Mestermann S., Webb G., Sp ttl T., Andus T., Sch lmerich J., HerfarthH., Ray K. and Falk W., Toll-like receptors2and4are up-regulated during intestinal inflammation.Gastroenterology2002,122(7):1987-2000
56. Herman J. G., Civin C. I., Issa J. P., Collector M. I., Sharkis S. J. and Baylin S. B., Distinct patternsof inactivation of p15INK4B and p16INK4A characterize the major types of hematologicalmalignancies. Cancer Res1997,57(5):837-841
57. Higuchi M., Matsuo A., Shingai M., Shida K., Ishii A., Funami K., Suzuki Y., Oshiumi H.,Matsumoto M. and Seya T., Combinational recognition of bacterial lipoproteins and peptidoglycanby chicken Toll-like receptor2subfamily. Dev Comp Immunol2008,32(2):147-155
58. Hisano M., Ohta H., Nishimune Y. and Nozaki M., Methylation of CpG dinucleotides in the openreading frame of a testicular germ cell-specific intronless gene, Tact1/Actl7b, represses itsexpression in somatic cells. Nucleic Acids Res2003,31(16):4797-4804
59. Hu J. X., Bumstead N., Barrow P., Sebastiani G., Olien L., Morgan K. and Malo D., Resistance tosalmonellosis in the chicken is linked to NRAMP1and TNC. Genome Research1997,7(7):693-704
60. Hubert F. X., Voisine C., Louvet C., Heslan J. M., Ouabed A., Heslan M. and Josien R.,Differential pattern recognition receptor expression but stereotyped responsiveness in rat spleendendritic cell subsets. The Journal of Immunology2006,177(2):1007-1016
61. Iqbal M., Philbin V. J., Withanage G. S. K., Wigley P., Beal R. K., Goodchild M. J., Barrow P.,McConnell I., Maskell D. J., Young J., Bumstead N., Boyd Y. and Smith A. L., Identification andfunctional characterization of chicken Toll-like receptor5reveals a fundamental role in the biologyof infection with Salmonella enterica serovar typhimurium. Infection and immunity2005,73(4):2344-2350
62. Isaacs A. and Lindenmann J., Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci1957,147(927):258-267
63. Jakobsson J., Cordero M. I., Bisaz R., Groner A. C., Busskamp V., Bensadoun J. C., Cammas F.,Losson R., Mansuy I. M., Sandi C. and Trono D., KAP1-mediated epigenetic repression in theforebrain modulates behavioral vulnerability to stress. Neuron2008,60(5):818-831
64. Jirtle R. L., Genomic imprinting and cancer. Experimental Cell Research1999,248(1):18-24
65. Kabelitz D., Expression and function of Toll-like receptors in T lymphocytes. Curr Opin Immunol2007,19(1):39-45
66. Katso R., Okkenhaug K., Ahmadi K., White S., Timms J. and Waterfield M. D., Cellular functionof phosphoinositide3-kinases: Implications for development, immunity, homeostasis, and cancer.Annual Review of Cell and Developmental Biology2001,17(615-675
67. Kawai T. and Akira S., TLR signaling. Seminars in Immunology2007,19(1):24-32
68. Keestra A. M., de Zoete M. R., van Aubel R. A. and van Putten J. P., The central leucine-rich repeatregion of chicken TLR16dictates unique ligand specificity and species-specific interaction withTLR2. J Immunol2007,178(11):7110-7119
69. Kenny E. F. and O'Neill L. A. J., Signalling adaptors used by Toll-like receptors: An update.Cytokine2008,43(3):342-349
70. Kinjyo I., Hanada T., Inagaki-Ohara K., Mori H., Aki D., Ohishi M., Yoshida H., Kubo M. andYoshimura A., SOCS1/JAB is a negative regulator of LPS-induced macrophage activation.Immunity2002,17(5):583-591
71. Kogut M. H., Swaggerty C., He H. Q., Pevzner I. and Kaiser P., Toll-like receptor agonistsstimulate differential functional activation and cytokine and chemokine gene expression inheterophils isolated from chickens with differential innate responses. Microbes and Infection2006,8(7):1866-1874
72. Kondo T., Bobek M. P., Kuick R., Lamb B., Zhu X. X., Narayan A., Bourc'his D.,Viegas-Pequignot E., Ehrlich M. and Hanash S. M., Whole-genome methylation scan in ICFsyndrome: hypomethylation of non-satellite DNA repeats D4Z4and NBL2. Human MolecularGenetics2000,9(4):597-604
73. Kornberg R. D. and Lorch Y. L., Twenty-five years of the nucleosome, fundamental particle of theeukaryote chromosome. Cell1999,98(3):285-294
74. Kuroishi T., Tanaka Y., Sakai A., Sugawara Y., Komine K. I. and Sugawara S., Human parotidsaliva contains soluble toll-like receptor (TLR)2and modulates TLR2-mediated interleukin-8production by monocytic cells. Molecular Immunology2007,44(8):1969-1976
75. Lazarevic V., Nolt D. and Flynn J. A. L., Long-term control of Mycobacterium tuberculosisinfection is mediated by dynamic immune responses. Journal of Immunology2005,175(2):1107-1117
76. Leveque G., Forgetta V., Morroll S., Smith A. L., Bumstead N., Barrow P., Loredo-Osti J., MorganK. and Malo D., Allelic variation in TLR4is linked to susceptibility to Salmonella enterica serovarTyphimurium infection in chickens. Infection and immunity2003a,71(3):1116-1124
77. Leveque G., Forgetta V., Morroll S., Smith A. L., Bumstead N., Barrow P., Loredo-Osti J. C.,Morgan K. and Malo D., Allelic variation in TLR4is linked to susceptibility to Salmonella entericaserovar Typhimurium infection in chickens. Infect Immun2003b,71(3):1116-1124
78. Li P., Xia P., Wen J., Zheng M., Chen J., Zhao J., Jiang R., Liu R. and Zhao G., Up-regulation ofthe MyD88-dependent pathway of TLR signaling in spleen and caecum of young chickens infectedwith Salmonella serovar Pullorum. Vet Microbiol2010,143(2-4):346-351
79. Liew F. Y., Xu D., Brint E. K. and O'Neill L. A., Negative regulation of toll-like receptor-mediatedimmune responses. Nat Rev Immunol2005a,5(6):446-458
80. Liew F. Y., Xu D. M., Brint E. K. and O'Neill L. A. J., Negative regulation of Toll-likereceptor-mediated immune responses. Nature Reviews Immunology2005b,5(6):446-458
81. Lindell K. A., Saeed A. M. and McCabe G. P., Evaluation of resistance of four strains ofcommercial laying hens to experimental infection with Salmonella enteritidis phage type eight.Poult Sci1994,73(6):757-762
82. Liu P. T., Stenger S., Li H. Y., Wenzel L., Tan B. H., Krutzik S. R., Ochoa M. T., Schauber J., WuK., Meinken C., Kamen D. L., Wagner M., Bals R., Steinmeyer A., Zugel U., Gallo R. L.,Eisenberg D., Hewison M., Hollis B. W., Adams J. S., Bloom B. R. and Modlin R. L., Toll-likereceptor triggering of a vitamin D-mediated human antimicrobial response. Science2006,311(5768):1770-1773
83. Liu Y., Wang Y., Yamakuchi M., Isowaki S., Nagata E., Kanmura Y., Kitajima I. and Maruyama I.,Upregulation of toll-like receptor2gene expression in macrophage response to peptidoglycan andhigh concentration of lipopolysaccharide is involved in NF-κB activation. Infection and immunity2001,69(5):2788-2796
84. Lo P. K. and Sukumar S., Epigenomics and breast cancer. Pharmacogenomics2008,9(12):1879-1902
85. Lorenz E., Mira J. P., Frees K. L. and Schwartz D. A., Relevance of mutations in the TLR4receptor in patients with gram-negative septic shock. Arch Intern Med2002,162(9):1028-1032
86. MacLeod H. and Wetzler L. M., T cell activation by TLRs: a role for TLRs in the adaptive immuneresponse. Sci STKE2007,2007(402): pe48
87. Mansell A., Smith R., Doyle S. L., Gray P., Fenner J. E., Crack P. J., Nicholson S. E., Hilton D. J.,O'Neill L. A. J. and Hertzog P. J., Suppressor of cytokine signaling1negatively regulates Toll-likereceptor signaling by mediating Mal degradation. Nature immunology2006,7(2):148-155
88. Maris N. A., Dessing M. C., de Vos A. F., Bresser P., van der Zee J. S., Jansen H. M., Spek C. A.and van der Poll T., Toll-like receptor mRNA levels in alveolar macrophages after inhalation ofendotoxin. Eur Respir J2006,28(3):622-626
89. Martin-Subero J. I. and Esteller M., Profiling Epigenetic Alterations in Disease. EpigeneticContributions in Autoimmune Disease2011,711(162-177
90. Martin M. U. and Wesche H., Summary and comparison of the signaling mechanisms of theToll/interleukin-1receptor family. Biochim Biophys Acta2002,1592(3):265-280
91. Matarazzo M. R., Boyle S., D'Esposito M. and Bickmore W. A., Chromosome territoryreorganization in a human disease with altered DNA methylation. Proceedings of the NationalAcademy of Sciences of the United States of America2007,104(42):16546-16551
92. McLoughlin M., Mcllroy S. and Neill S., A major outbreak of botulism in cattle being fed ensiledpoultry litter. Veterinary Record1988,122(24):579-581
93. Medzhitov R. and Janeway C. A., Innate immunity: The virtues of a nonclonal system ofrecognition. Cell1997,91(3):295-298
94. Melmed G., Thomas L. S., Lee N., Tesfay S. Y., Lukasek K., Michelsen K. S., Zhou Y. H., Hu B.,Arditi M. and Abreu M. T., Human intestinal epithelial cells are broadly unresponsive to toll-likereceptor2-dependent bacterial ligands: Implications for host-microbial interactions in the gut.Journal of Immunology2003,170(3):1406-1415
95. Monack D. M., Mueller A. and Falkow S., Persistent bacterial infections: the interface of thepathogen and the host immune system. Nat Rev Microbiol2004,2(9):747-765
96. Morison I. M. and Reeve A. E., A catalogue of imprinted genes and parent-of-origin effects inhumans and animals. Human Molecular Genetics1998,7(10):1599-1609
97. Nadkarni M. A., Martin F. E., Jacques N. A. and Hunter N., Determination of bacterial load byreal-time PCR using a broad-range (universal) probe and primers set. Microbiology2002,148(Pt1):257-266
98. Naiki Y., Michelsen K. S., Schroder N. W. J., Alsabeh R., Slepenkin A., Zhang W. X., Chen S., WeiB., Bulut Y., Wong M. H., Peterson E. M. and Arditi M., MyD88is pivotal for the earlyinflammatory response and subsequent bacterial clearance and survival in a mouse model ofChlamydia pneumoniae pneumonia. Journal of Biological Chemistry2005a,280(32):29242-29249
99. Naiki Y., Michelsen K. S., Zhang W., Chen S., Doherty T. M. and Arditi M., Transforming growthfactor-beta differentially inhibits MyD88-dependent, but not TRAM-and TRIF-dependent,lipopolysaccharide-induced TLR4signaling. J Biol Chem2005b,280(7):5491-5495
100. Naka T., Matsumoto T., Narazaki M., Fujimoto M., Morita Y., Ohsawa Y., Saito H., Nagasawa T.,Uchiyama Y. and Kishimoto T., Accelerated apoptosis of lymphocytes by augmented induction ofBax in SSI-1(STAT-induced STAT inhibitor-1) deficient mice. Proc Natl Acad Sci U S A1998,95(26):15577-15582
101. Nakagawa R., Naka T., Tsutsui H., Fujimoto M., Kimura A., Abe T., Seki E., Sato S., Takeuchi O.and Takeda K., SOCS-1participates in negative regulation of LPS responses. Immunity2002a,17(5):677-687
102. Nakagawa R., Naka T., Tsutsui H., Fujimoto M., Kimura A., Abe T., Seki E., Sato S., Takeuchi O.,Takeda K., Akira S., Yamanishi K., Kawase I., Nakanishi K. and Kishimoto T., SOCS-1participates in negative regulation of LPS responses. Immunity2002b,17(5):677-687
103. Nakayama M., Wada M., Harada T., Nagayama J., Kusaba H., Ohshima K., Kozuru M., KomatsuH., Ueda R. and Kuwano M., Hypomethylation status of CpG sites at the promoter region andoverexpression of the human MDR1gene in acute myeloid leukemias. Blood1998,92(11):4296-4307
104. Nerren J. R., He H. Q., Genovese K. and Kogut M. H., Expression of the avian-specific toll-likereceptor15in chicken heterophils is mediated by Gram-negative and Gram-positive bacteria, butnot TLR agonists. Veterinary Immunology and Immunopathology2010,136(1-2):151-156
105. Nguyen T. H., Mai N. L., Le T. P., Ha V., Nguyen T. C., Tran T. H., Farrar J. J. and Dunstan S. J.,Toll-like receptor4(TLR4) and typhoid fever in Vietnam. PLoS One2009,4(3): e4800
106. Palmer B. R. and Marinus M. G., The dam and dcm strains of Escherichia coli--a review. Gene1994,143(1):1-12
107. Philbin V. J., Iqbal M., Boyd Y., Goodchild M. J., Beal R. K., Bumstead N., Young J. and Smith A.L., Identification and characterization of a functional, alternatively spliced Toll-like receptor7(TLR7) and genomic disruption of TLR8in chickens. Immunology2005,114(4):507-521
108. Poltorak A., He X., Smirnova I., Liu M. Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M.,Galanos C., Freudenberg M., Ricciardi-Castagnoli P., Layton B. and Beutler B., Defective LPSsignaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4gene. Science1998,282(5396):2085-2088
109. Pothlichet J., Chignard M. and Si-Tahar M., Cutting edge: innate immune response triggered byinfluenza A virus is negatively regulated by SOCS1and SOCS3through aRIG-I/IFNAR1-dependent pathway. J Immunol2008a,180(4):2034-2038
110. Pothlichet J., Chignard M. and Si-Tahar M., Innate immune response triggered by influenza a virusis negatively regulated by SOCS1and SOCS3through a RIG-I/IFNARI-dependent pathway.Journal of Immunology2008b,180(4):2034-2038
111. Re F. and Strominger J. L., IL-10released by concomitant TLR2stimulation blocks the inductionof a subset of Th1cytokines that are specifically induced by TLR4or TLR3in human dendriticcells. J Immunol2004,173(12):7548-7555
112. Renn C. N., Sanchez D. J., Ochoa M. T., Legaspi A. J., Oh C. K., Liu P. T., Krutzik S. R., Sieling P.A., Cheng G. and Modlin R. L., TLR activation of Langerhans cell-like dendritic cells triggers anantiviral immune response. The Journal of Immunology2006,177(1):298-305
113. Ruprecht C. R. and Lanzavecchia A., Toll‐like receptor stimulation as a third signal required foractivation of human naive B cells. European journal of immunology2006,36(4):810-816
114. Sadeyen J. R., Trotereau J., Protais J., Beaumont C., Sellier N., Salvat G., Velge P. and LalmanachA. C., Salmonella carrier-state in hens: study of host resistance by a gene expression approach.Microbes and Infection2006,8(5):1308-1314
115. Schwarz H., Schneider K., Ohnemus A., Lavric M., Kothlow S., Bauer S., Kaspers B. and StaeheliP., Chicken toll-like receptor3recognizes its cognate ligand when ectopically expressed in humancells. J Interferon Cytokine Res2007,27(2):97-101
116. Shilatifard A., Chromatin modifications by methylation and ubiquitination: Implications in theregulation of gene expression. Annual Review of Biochemistry2006,75(243-269
117. Shuto T., Furuta T., Oba M., Xu H. D., Li J. D., Cheung J., Gruenert D. C., Uehara A., Suico M. A.,Okiyoneda T. and Kai H., Promoter hypomethylation of Toll-like receptor-2gene is associated withincreased proinflammatory response toward bacterial peptidoglycan in cystic fibrosis bronchialepithelial cells. Faseb Journal2006,20(2):782-+
118. Smith-Vaughan H., Byun R., Nadkarni M., Jacques N. A., Hunter N., Halpin S., Morris P. S. andLeach A. J., Measuring nasal bacterial load and its association with otitis media. BMC Ear NoseThroat Disord2006,6(10
119. Sripathy S. P., Stevens J. and Schultz D. C., The KAP1corepressor functions to coordinate theassembly of de novo HP1-demarcated microenvironments of heterochromatin required for KRABzinc finger protein-mediated transcriptional repression. Mol Cell Biol2006,26(22):8623-8638
120. Starr R., Metcalf D., Elefanty A. G., Brysha M., Willson T. A., Nicola N. A., Hilton D. J. andAlexander W. S., Liver degeneration and lymphoid deficiencies in mice lacking suppressor ofcytokine signaling-1. Proceedings of the National Academy of Sciences1998,95(24):14395
121. Sun S., Wang X., Wu X., Zhao Y., Wang F., Liu X., Song Y., Wu Z. and Liu M., Toll-like receptoractivation by helminths or helminth products to alleviate inflammatory bowel disease. ParasitVectors2011,4(186
122. Suter C. M., Martin D. I. and Ward R. L., Hypomethylation of L1retrotransposons in colorectalcancer and adjacent normal tissue. Int J Colorectal Dis2004,19(2):95-101
123. Suzuki N., Suzuki S., Duncan G. S., Millar D. G., Wada T., Mirtsos C., Takada H., Wakeham A.,Itie A. and Li S., Severe impairment of interleukin-1and Toll-like receptor signalling in micelacking IRAK-4. Nature2002,416(6882):750-756
124. Takahashi K., Sugi Y., Hosono A. and Kaminogawa S., Epigenetic regulation of TLR4geneexpression in intestinal epithelial cells for the maintenance of intestinal homeostasis. The Journalof Immunology2009a,183(10):6522-6529
125. Takahashi K., Sugi Y., Hosono A. and Kaminogawa S., Epigenetic Regulation of TLR4GeneExpression in Intestinal Epithelial Cells for the Maintenance of Intestinal Homeostasis. Journal ofImmunology2009b,183(10):6522-6529
126. Takeda K. and Akira S., Toll-like receptors in innate immunity. International immunology2005,17(1):1-14
127. Temperley N. D., Berlin S., Paton I. R., Griffin D. K. and Burt D. W., Evolution of the chickenToll-like receptor gene family: a story of gene gain and gene loss. BMC genomics2008,9(1):62
128. Thoma-Uszynski S., Stenger S., Takeuchi O., Ochoa M. T., Engele M., Sieling P. A., Barnes P. F.,Rollinghoff M., Bolcskei P. L., Wagner M., Akira S., Norgard M. V., Belisle J. T., Godowski P. J.,Bloom B. R. and Modlin R. L., Induction of direct antimicrobial activity through mammaliantoll-like receptors. Science2001,291(5508):1544-1547
129. Tycko B., Epigenetic gene silencing in cancer. J Clin Invest2000,105(4):401-407
130. Ulevitch R. J. and Tobias P. S., Receptor-dependent mechanisms of cell stimulation by bacterialendotoxin. Annu Rev Immunol1995,13(437-457
131. van Hemert S., Hoekman A. J., Smits M. A. and Rebel J. M., Immunological and gene expressionresponses to a Salmonella infection in the chicken intestine. Vet Res2007,38(1):51-63
132. van Oers N. S. and Chen Z. J., Cell biology. Kinasing and clipping down the NF-kappa B trail.Science2005,308(5718):65-66
133. Vanden Eijnden S., Goriely S., De Wit D., Goldman M. and Willems F., Preferential production ofthe IL‐12(p40)/IL‐23(p19) heterodimer by dendritic cells from human newborns. Europeanjournal of immunology2006,36(1):21-26
134. Vanden E. S., Goriely S., De Wit D., Goldman M. and Willems F., Preferential production of theIL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns. European journal ofimmunology2006,36(1):21
135. Vanselow J., Yang W., Herrmann J., Zerbe H., Schuberth H. J., Petzl W., Tomek W. and Seyfert H.M., DNA-remethylation around a STAT5-binding enhancer in the αS1-casein promoter isassociated with abrupt shutdown of αS1-casein synthesis during acute mastitis. Journal ofmolecular endocrinology2006,37(3):463-477
136. Vicente J., Higgins S., Bielke L., Tellez G., Donoghue D., Donoghue A. and Hargis B., Effect ofprobiotic culture candidates on Salmonella prevalence in commercial turkey houses. Journal ofApplied Poultry Research2007,16(3):471-476
137. Wang N., Strugnell R., Wijburg O. and Brodnicki T., Measuring Bacterial Load and ImmuneResponses in Mice Infected with Listeria monocytogenes. J Vis Exp2011,(54): e30761-8
138. Waterer G. and Rello J., Why should we measure bacterial load when treating community-acquiredpneumonia? Current Opinion in Infectious Diseases2011,24(2):137-141
139. Weighardt H., Kaiser-Moore S., Vabulas R. M., Kirschning C. J., Wagner H. and Holzmann B.,Cutting edge: myeloid differentiation factor88deficiency improves resistance against sepsiscaused by polymicrobial infection. The Journal of Immunology2002,169(6):2823-2827
140. Weiss D. S., Raupach B., Takeda K., Akira S. and Zychlinsky A., Toll-like receptors are temporallyinvolved in host defense. J Immunol2004,172(7):4463-4469
141. White D. G., Zhao S., Sudler R., Ayers S., Friedman S., Chen S., McDermott P. F., McDermott S.,Wagner D. D. and Meng J. H., The isolation of antibiotic-resistant Salmonella from retail groundmeats. New England Journal of Medicine2001,345(16):1147-1154
142. Wille-Reece U., Flynn B. J., Loré K., Koup R. A., Miles A. P., Saul A., Kedl R. M., Mattapallil J. J.,Weiss W. R. and Roederer M., Toll-like receptor agonists influence the magnitude and quality ofmemory T cell responses after prime-boost immunization in nonhuman primates. The Journal ofexperimental medicine2006,203(5):1249-1258
143. Wiznerowicz M., Jakobsson J., Szulc J., Liao S., Quazzola A., Beermann F., Aebischer P. andTrono D., The Kruppel-associated box repressor domain can trigger de Novo promoter methylationduring mouse early embryogenesis. Journal of Biological Chemistry2007,282(47):34535-34541
144. Yang H., Wei J., Zhang H., Lin L., Zhang W. and He S., Upregulation of Toll-like receptor (TLR)expression and release of cytokines from P815mast cells by GM-CSF. BMC Cell Biol2009,10(37
145. Yang H., Wei J., Zhang H., Song W., Wei W., Zhang L., Qian K. and He S., Upregulation ofToll-like Receptor (TLR) expression and release of cytokines from mast cells by IL-12. CellPhysiol Biochem2010,26(3):337-346
146. Yoshida H., Jono H., Kai H. and Li J. D., The tumor suppressor cylindromatosis (CYLD) acts as anegative regulator for toll-like receptor2signaling via negative cross-talk with TRAF6and TRAF7.Journal of Biological Chemistry2005,280(49):41111-41121
147. Zhang G. L. and Ghosh S., Negative regulation of toll-like receptor-mediated signaling by Tollip.Journal of Biological Chemistry2002,277(9):7059-706
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