title: The Bacterial T6SS Effector EvpP Prevents NLRP3 Inflammasome Activation by Inhibiting the Ca2+-Dependent MAPK-Jnk Pathway.
abstract: 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.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Dahai
authors.initials: D
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Fajun
authors.initials: F
authors.lastname: Han
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China.
authors.forename: Jingfan
authors.initials: J
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China.
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. Electronic address: qinliu@ecust.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D020609:Edwardsiella tarda / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D007739:L Cells; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D000069296:Type III Secretion Systems / Q000378:metabolism*; D000069376:Type VI Secretion Systems / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D058847:Inflammasomes; C512299:Ipaf protein, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D000069296:Type III Secretion Systems; D000069376:Type VI Secretion Systems; D037521:Virulence Factors; D048031:JNK Mitogen-Activated Protein Kinases
keywords: ASC oligomerization; Jnk; NLRP3 inflammasome; T6SS effector; calcium