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Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection

Authors :
Yu Guo
Rudi Mao
Qingqing Xie
Xiaojie Cheng
Tao Xu
Xiaoyuan Wang
Yan Du
Xiaopeng Qi
Source :
Frontiers in Cell and Developmental Biology, Vol 9 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

Bacterial infection tendentiously triggers inflammasome activation, whereas the roles of inflammasome activation in host defense against diverse infections remain unclear. Here, we identified that an ASC-dependent inflammasome activation played opposite roles in host defense against Francisella novicida wild-type (WT) U112 and mutant strain XWK4. Comparing with U112, XWK4 infection induced robust cytokine production, ASC-dependent inflammasome activation, and pyroptosis. Both AIM2 and NLRP3 were involved and played independent roles in XWK4-induced inflammasome activation. Type II interferon was partially required for XWK4-triggered inflammasome activation, which was different from type I interferon dependency in U112-induced inflammasome activation. Distinct from F. novicida U112 and Acinetobacter baumannii infection, Asc–/– mice were more resistant than WT mice response to XWK4 infection by limiting bacterial burden in vivo. The excessive inflammasome activation triggered by XWK4 infection caused dramatical cell death and pathological damage. Our study offers novel insights into mechanisms of inflammasome activation in host defense and provides potential therapeutic approach against bacterial infections and inflammatory diseases.

Details

Language :
English
ISSN :
2296634X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cell and Developmental Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.25f9f56fa42e4f47a6087e827c382998
Document Type :
article
Full Text :
https://doi.org/10.3389/fcell.2021.743335