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STING Contributes to Host Defense Against Staphylococcus aureus Pneumonia Through Suppressing Necroptosis.

Authors :
Liu ZZ
Yang YJ
Zhou CK
Yan SQ
Ma K
Gao Y
Chen W
Source :
Frontiers in immunology [Front Immunol] 2021 May 31; Vol. 12, pp. 636861. Date of Electronic Publication: 2021 May 31 (Print Publication: 2021).
Publication Year :
2021

Abstract

STING (Stimulator of interferon genes) is known as an important adaptor protein or direct sensor in the detection of nucleotide originating from pathogens or the host. The implication of STING during pulmonary microbial infection remains unknown to date. Herein, we showed that STING protected against pulmonary S.aureus infection by suppressing necroptosis. STING deficiency resulted in increased mortality, more bacteria burden in BALF and lungs, severe destruction of lung architecture, and elevated inflammatory cells infiltration and inflammatory cytokines secretion. STING deficiency also had a defect in bacterial clearance, but did not exacerbate pulmonary inflammation during the early stage of infection. Interestingly, TUNEL staining and LDH release assays showed that STING <superscript>-/-</superscript> mice had increased cell death than WT mice. We further demonstrated that STING <superscript>-/-</superscript> mice had decreased number of macrophages accompanied by increased dead macrophages. Our in vivo and in vitro findings further demonstrated this cell death as necroptosis. The critical role of necroptosis was detected by the fact that MLKL <superscript>-/-</superscript> mice exhibited decreased macrophage death and enhanced host defense to S.aureus infection. Importantly, blocking necroptosis activation rescued host defense defect against S.aureus pneumonia in STING <superscript>-/-</superscript> mice. Hence, these results reveal an important role of STING in suppressing necroptosis activation to facilitate early pathogen control during pulmonary S.aureus infection.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Liu, Yang, Zhou, Yan, Ma, Gao and Chen.)

Details

Language :
English
ISSN :
1664-3224
Volume :
12
Database :
MEDLINE
Journal :
Frontiers in immunology
Publication Type :
Academic Journal
Accession number :
34135886
Full Text :
https://doi.org/10.3389/fimmu.2021.636861