Activation of NLRC4 downregulates TLR5-mediated antibody immune responses against flagellin
Activation of NLRC4 downregulates TLR5-mediated antibody immune responses against flagellin
复制标题
NLRC4的激活下调TLR5介导的针对鞭毛蛋白的抗体免疫反应
DOI：
10.1038/cmi.2015.33
复制
发表时间：
2016-07-01
影响因子：
24.1
通讯作者：
Yan, Huimin
中科院分区：
文献类型：
--
作者：
Li, Wei;Yang, Jingyi;Yan, Huimin
细菌鞭毛蛋白是一种独特的病原体相关分子模式（PAMP），可被细菌表面Toll样受体5（TLR 5）和胞浆NOD-like受体蛋白4（NLR）识别。鞭毛蛋白对TLR 5和/或NLRC 4信号通路的激活以及由此产生的免疫应答在抗细菌免疫中起重要作用。然而，目前还不清楚鞭毛蛋白激活TLR 5和/或NLRC 4信号通路的双重活性如何协调免疫应答。在这项研究中，我们评估了鞭毛蛋白及其突变体缺乏激活TLR 5和NLRC 4单独或组合的能力对鞭毛蛋白的适应性免疫应答的影响。不能激活NLRC 4的鞭毛蛋白比野生型鞭毛蛋白诱导显著更高的抗体应答。当体内巨噬细胞被耗尽时，可以消除增加的抗体应答。NLRC 4被鞭毛蛋白激活后下调了鞭毛蛋白诱导的和TLR 5介导的针对鞭毛蛋白的免疫应答。
Bacterial flagellin is a unique pathogen-associated molecular pattern (PAMP), which can be recognized by surface localized Toll-like receptor 5 (TLR5) and the cytosolic NOD-like receptor (NLR) protein 4 (NLRC4) receptors. Activation of the TLR5 and/or NLRC4 signaling pathways by flagellin and the resulting immune responses play important roles in anti-bacterial immunity. However, it remains unclear how the dual activities of flagellin that activate the TLR5 and/or NLRC4 signaling pathways orchestrate the immune responses. In this study, we assessed the effects of flagellin and its mutants lacking the ability to activate TLR5 and NLRC4 alone or in combination on the adaptive immune responses against flagellin. Flagellin that was unable to activate NLRC4 induced a significantly higher antibody response than did wild-type flagellin. The increased antibody response could be eliminated when macrophages were depleted in vivo. The activation of NLRC4 by flagellin downregulated the flagellin-induced and TLR5-mediated immune responses against flagellin.