AUTHOR=Gao Yue , Xu Wenchun , Dou Xiaoyun , Wang Hong , Zhang Xuemei , Yang Shenghui , Liao Hongyi , Hu Xuexue , Wang Hong 

TITLE=Mitochondrial DNA Leakage Caused by Streptococcus pneumoniae Hydrogen Peroxide Promotes Type I IFN Expression in Lung Cells

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00630

DOI=10.3389/fmicb.2019.00630

ISSN=1664-302X

ABSTRACT=<p><italic>Streptococcus pneumoniae (S. pn)</italic>, the bacterial pathogen responsible for invasive pneumococcal diseases, is capable of producing substantial amounts of hydrogen peroxide. However, the impact of <italic>S. pn</italic>-secreted hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) on the host immune processes is not completely understood. Here, we demonstrated that <italic>S. pn</italic>-secreted H<sub>2</sub>O<sub>2</sub> caused mitochondrial damage and severe histopathological damage in mouse lung tissue. Additionally, <italic>S. pn</italic>-secreted H<sub>2</sub>O<sub>2</sub> caused not only oxidative damage to mitochondrial deoxyribonucleic acid (mtDNA), but also a reduction in the mtDNA content in alveolar epithelia cells. This resulted in the release of mtDNA into the cytoplasm, which subsequently induced type I interferons (IFN-I) expression. We also determined that stimulator of interferon genes (STING) signaling was probably involved in <italic>S. pn</italic> H<sub>2</sub>O<sub>2</sub>-inducing IFN-I expression in response to mtDNA damaged by <italic>S. pn</italic>-secreted H<sub>2</sub>O<sub>2</sub>. In conclusion, our study demonstrated that H<sub>2</sub>O<sub>2</sub> produced by <italic>S. pn</italic> resulted in mtDNA leakage from damaged mitochondria and IFN-I production in alveolar epithelia cells, and STING may be required in this process, and this is a novel mitochondrial damage mechanism by which <italic>S. pn</italic> potentiates the IFN-I cascade in <italic>S. pn</italic> infection.</p>