Li Wei, Yang Jingyi, Zhang Ejuan, Zhong Maohua, Xiao Yang, Yu Jie, Zhou Dihan, Cao Yuan, Yang Yi, Li Yaoming, Yan Huimin
Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, People's Republic of China.
Cell Mol Immunol. 2016 Jul;13(4):514-23. doi: 10.1038/cmi.2015.33. Epub 2015 Apr 27.
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.
细菌鞭毛蛋白是一种独特的病原体相关分子模式（PAMP），可被表面定位的Toll样受体5（TLR5）和胞质NOD样受体（NLR）蛋白4（NLRC4）受体识别。鞭毛蛋白激活TLR5和/或NLRC4信号通路以及由此产生的免疫反应在抗菌免疫中发挥重要作用。然而，尚不清楚激活TLR5和/或NLRC4信号通路的鞭毛蛋白的双重活性如何协调免疫反应。在本研究中，我们评估了鞭毛蛋白及其单独或联合缺乏激活TLR5和NLRC4能力的突变体对针对鞭毛蛋白的适应性免疫反应的影响。无法激活NLRC4的鞭毛蛋白诱导的抗体反应明显高于野生型鞭毛蛋白。当体内巨噬细胞被清除时，增加的抗体反应可以消除。鞭毛蛋白对NLRC4的激活下调了鞭毛蛋白诱导的和TLR5介导的针对鞭毛蛋白的免疫反应。
