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

, the bacterial pathogen responsible for invasive pneumococcal diseases, is capable of producing substantial amounts of hydrogen peroxide. However, the impact of -secreted hydrogen peroxide (H O ) on the host immune processes is not completely understood. Here, we demonstrated that -secreted H O caused mitochondrial damage and severe histopathological damage in mouse lung tissue. Additionally, -secreted H O 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 H O -inducing IFN-I expression in response to mtDNA damaged by -secreted H O . In conclusion, our study demonstrated that H O produced by 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 potentiates the IFN-I cascade in infection.