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

摘要

Streptococcus pneumoniae (S. pn) , the bacterial pathogen responsible for invasive pneumococcal diseases, is capable of producing substantial amounts of hydrogen peroxide. However, the impact of S. pn -secreted hydrogen peroxide (H _(2)O _(2)) on the host immune processes is not completely understood. Here, we demonstrated that S. pn -secreted H _(2)O _(2) caused mitochondrial damage and severe histopathological damage in mouse lung tissue. Additionally, S. pn -secreted H _(2)O _(2) 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 S. pn H _(2)O _(2)-inducing IFN-I expression in response to mtDNA damaged by S. pn -secreted H _(2)O _(2). In conclusion, our study demonstrated that H _(2)O _(2) produced by S. pn 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 S. pn potentiates the IFN-I cascade in S. pn infection.