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STING Contributes to Host Defense Against Staphylococcus aureus Pneumonia Through Suppressing Necroptosis.
- 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
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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.)
- Subjects :
- Animals
Bacterial Load
Cells, Cultured
Cytokines metabolism
Immunity
Inflammation Mediators metabolism
Lung microbiology
Membrane Proteins genetics
Mice
Mice, Inbred C57BL
Necroptosis
Protein Kinases genetics
Lung pathology
Macrophages immunology
Membrane Proteins metabolism
Pneumonia, Staphylococcal immunology
Protein Kinases metabolism
Staphylococcal Infections immunology
Staphylococcus aureus physiology
Subjects
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