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Type I IFN expression is stimulated by cytosolic Mt DNA released from pneumolysin‐damaged mitochondria via the STING signaling pathway in macrophages
Author(s) -
Hu Xuexue,
Peng Xiaoqiong,
Lu Chang,
Zhang Xuemei,
Gan Lingling,
Gao Yue,
Yang Shenghui,
Xu Wenchun,
Wang Jian,
Yin Yibing,
Wang Hong
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15001
Subject(s) - pneumolysin , interferon , mitochondrion , recombinant dna , cytosol , stimulator of interferon genes , signal transduction , microbiology and biotechnology , biology , polyglutamic acid , streptococcus pneumoniae , chemistry , gene , innate immune system , immunology , immune system , biochemistry , antibiotics , enzyme
Pneumolysin (Ply), a major virulence factor of Streptococcus pneumoniae (S. pn) , affects the immunity of host cells during infection. It has been reported that Ply is involved in S. pn standard strain D39‐induced interferon‐β ( IFN ‐β) expression; however, other findings suggest that recombinant Ply protein is incapable of triggering IFN ‐β expression. Here, we demonstrated that purified Ply was capable of initiating oxidative damage to mitochondria, resulting in the subsequent release of mitochondrial deoxyribonucleic acid (mt DNA ), which mediated IFN ‐β expression in macrophages. Importantly, we determined that IFN ‐β expression was regulated by stimulator of interferon genes ( STING ) signaling in response to Ply. In conclusion, our study identified that IFN ‐β production was triggered by Ply in macrophages and mt DNA released from Ply‐damaged mitochondria mediated this process, through the STING pathway. This is a novel mechanism by which S. pn modulates type I IFN response in macrophages.