文献类型：期刊文献

英文题名：The Bacterial T6SS Effector EvpP Prevents NLRP3 Inflammasome Activation by Inhibiting the Ca2+-Dependent MAPK-Jnk Pathway

作者：Chen, Hao[1];Yang, Dahai[1];Han, Fajun[1];Tan, Jinchao[1];Zhang, Lingzhi[1];Xiao, Jingfan[1,2];Zhang, Yuanxing[1,2,3];Liu, Qin[1,2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Engn Res Ctr Maricultured Anim Vaccines, Shanghai 200237, Peoples R China;[3]Shanghai Collaborat Innovat Ctr Biomfg Technol, Shanghai 200237, Peoples R China

年份：2017

卷号：21

期号：1

起止页码：47

外文期刊名：CELL HOST & MICROBE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000392843900008)】；

基金：We thank Feng Shao from the National Institute of Biological Science, Beijing (NIBS) for providing gene-KO mice and helpful suggestions, and thank Gabriel Nunez and Yuan He from the University of Michigan for instructive discussions and technical assistance. This work was supported by the NSFC grants 31430090 to Y.Z., 31472308 to Q.L., and 31622059 to Q.L.

语种：英文

摘要：Inflammasome activation is an important innate immune defense mechanism against bacterial infection, and in return, bacteria express virulence determinants that counteract inflammasome activation. Many such effectors are secreted into host cells via specialized bacterial secretion systems. Here, the intracellular pathogenic bacterium Edwardsiella tarda was demonstrated to activate NLRC4 and NLRP3 inflammasomes via a type III secretion system (T3SS), and to inhibit NLRP3 inflammasome via a type VI secretion system (T6SS), indicating the antagonistic roles of these systems in inflammasome signaling. Furthermore, a non-VgrG T6SS effector, EvpP, was identified that significantly inhibited NLRP3 inflammasome activation. Subsequent studies revealed that EvpP significantly suppressed Jnk activation, thus impairing oligomerization of the inflammasome adaptor ASC. Moreover, EvpP counteracted cytoplasmic Ca2+ increase, which works upstream of Jnk activation to regulate the NLRP3 inflammasome. Finally, EvpP-mediated inflammasome inhibition promoted bacterial colonization in vivo. This work expands our understanding of bacterial T6SS in counteracting host immune responses.