Epigenetic modification of TLRs in leukocytes is associated with increased susceptibility to Salmonella enteritidis in chickens.
Epigenetic modification of TLRs in leukocytes is associated with increased susceptibility to Salmonella enteritidis in chickens.
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DOI：
10.1371/journal.pone.0033627
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wen J
中科院分区：
文献类型：
--
作者：
Gou Z;Liu R;Zhao G;Zheng M;Li P;Wang H;Zhu Y;Chen J;Wen J
toll样受体（TLRs）信号通路是抵御肠炎沙门氏菌感染的第一道防线，但鸡对肠炎沙门氏菌感染易感性的分子机制尚不清楚。将注射肠炎沙门氏菌的SPF鸡分为两组，一组为沙门氏菌敏感鸡（注射后5 d内死亡，n = 6），另一组为6只注射后存活15 d的沙门氏菌抗性鸡。本研究表明，敏感鸡的细菌负荷显著高于耐药鸡，敏感鸡白细胞中TLR4、TLR2-1和TLR21的表达明显低于耐药鸡。诱导促炎细胞因子基因IL-6和IFN-β的表达在耐药鸡中显著增强，而在易感鸡中无显著增强。与TLR基因表达降低相比，锌指蛋白493 （ZNF493）基因和toll -相互作用蛋白（TOLLIP）基因在易感鸡中表达增强。最后，5- aza -2-脱氧胞苷（5-Aza-dc）处理后，体外感染肠炎沙门氏菌的外周血单核细胞（PBMCs）中TLR4的表达显著升高，而5-Aza-dc或trichostatin a均能有效上调TLR21和TLR2-1的表达。在易感鸡中，TLR4和TLR21基因预测启动子区域的DNA甲基化和TLR2-1基因外显子CpG岛显著高于抗性鸡。综上所述，结果表明，白细胞中与znf493相关的表观遗传修饰可能通过降低TLR4、TLR21和TLR2-1的表达和应答，导致鸡对肠炎链球菌的易感性增加。
Toll-like receptors (TLRs) signaling pathways are the first lines in defense against Salmonella enteritidis (S. enteritidis) infection but the molecular mechanism underlying susceptibility to S. enteritidis infection in chicken remains unclear. SPF chickens injected with S. enteritidis were partitioned into two groups, one consisted of those from Salmonella-susceptible chickens (died within 5 d after injection, n = 6), the other consisted of six Salmonella-resistant chickens that survived for 15 d after injection. The present study shows that the bacterial load in susceptible chickens was significantly higher than that in resistant chickens and TLR4, TLR2-1 and TLR21 expression was strongly diminished in the leukocytes of susceptible chickens compared with those of resistant chickens. The induction of expression of pro-inflammatory cytokine genes, IL-6 and IFN-β, was greatly enhanced in the resistant but not in susceptible chickens. Contrasting with the reduced expression of TLR genes, those of the zinc finger protein 493 (ZNF493) gene and Toll-interacting protein (TOLLIP) gene were enhanced in the susceptible chickens. Finally, the expression of TLR4 in peripheral blood mononuclear cells (PBMCs) infected in vitro with S. enteritidis increased significantly as a result of treatment with 5-Aza-2-deoxycytidine (5-Aza-dc) while either 5-Aza-dc or trichostatin A was effective in up-regulating the expression of TLR21 and TLR2-1. DNA methylation, in the predicted promoter region of TLR4 and TLR21 genes, and an exonic CpG island of the TLR2-1 gene was significantly higher in the susceptible chickens than in resistant chickens. Taken together, the results demonstrate that ZNF493-related epigenetic modification in leukocytes probably accounts for increased susceptibility to S. enteritidis in chickens by diminishing the expression and response of TLR4, TLR21 and TLR2-1.
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作者：
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