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

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Hao Chen, Dahai Yang, Fajun Han, Jinchao Tan, Lingzhi Zhang, Jingfan Xiao, Yuanxing Zhang, Qin Liu
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.

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Teaser

Edwardsiella tarda is an important pathogenic bacterium infecting a wide range of hosts from fish to humans. Chen et al. identify a novel T6SS effector, EvpP, in E. tarda that targets intracellular Ca²⁺ signaling to impair Jnk activation and subsequent ASC oligomerization, which promotes bacterial colonization in mice.


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