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Bacterial Type I CRISPR ‐Cas systems influence inflammasome activation in mammalian host by promoting autophagy
Author(s) -
Wu Qun,
Wang Biao,
Zhou Chuanmin,
Lin Ping,
Qin Shugang,
Gao Pan,
Wang Zhihan,
Xia Zhenwei,
Wu Min
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13108
Subject(s) - crispr , biology , inflammasome , autophagy , innate immune system , microbiology and biotechnology , acquired immune system , immune system , genetics , gene , receptor , apoptosis
Summary The clustered regularly interspaced short palindromic repeats ( CRISPR ) and CRISPR ‐associated systems ( CRISPR ‐Cas) systems in prokaryotes function at defending against foreign DNA s, providing adaptive immunity to maintain homeostasis. CRISPR ‐Cas may also influence immune regulation ability in mammalian cells through alterations of pathogenic extent and nature. Recent research has implied that Type I CRISPR ‐Cas systems of Pseudomonas aeruginosa strain UCBPP ‐ PA 14 impede recognition by Toll‐like receptor 4, and decrease pro‐inflammatory responses both in vitro and in vivo . However, the molecular mechanism by which CRISPR ‐Cas systems affect host immunity is largely undemonstrated. Here, we explored whether CRISPR ‐Cas systems can influence autophagy to alter the activation of inflammasome. Using the wild‐type PA 14 and total CRISPR ‐Cas region deletion (∆ TCR ) mutant strain, we elucidated the role and underlying mechanism of Type I CRISPR ‐Cas systems in bacterial infection, and showed that CRISPR ‐Cas systems impacted the release of mitochondrial DNA and induction of autophagy. CRISPR ‐Cas deficiency led to an increase of mitochondrial DNA release, a decrease in autophagy, an increase of inflammasome activation and, ultimately, an elevation of pro‐inflammatory response. Our findings illustrate a new important mechanism by which Type I CRISPR ‐Cas systems control their virulence potency to evade host defense.