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: Hao Chen, Dahai Yang, Fajun Han, Jinchao Tan, Lingzhi Zhang, Jingfan Xiao, Yuanxing Zhang, Qin Liu
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 21 Issue 1 Pg. 47-58 (Jan 11 2017) ISSN: 1934-6069 [Electronic] United States
• PMID: 28081443 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Calcium-Binding Proteins
• Inflammasomes
• Ipaf protein, mouse
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Type III Secretion Systems
• Type VI Secretion Systems
• Virulence Factors
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis Regulatory Proteins (metabolism)
• Calcium-Binding Proteins (metabolism)
• Cell Line, Tumor
• Edwardsiella tarda (immunology, metabolism)
• Enzyme Activation
• HEK293 Cells
• HeLa Cells
• Humans
• Inflammasomes (metabolism)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• L Cells
• MAP Kinase Signaling System (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Type III Secretion Systems (metabolism)
• Type VI Secretion Systems (metabolism)
• Virulence Factors (metabolism)