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Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
Published on: February 24, 2018
Mitochondrial DNA Leakage Caused by Streptococcus pneumoniae Hydrogen Peroxide Promotes Type I IFN Expression in Lung
Yue Gao1,2, Wenchun Xu1,2, Xiaoyun Dou3
1Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
Abstract:
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 (H2O2) on the host immune processes is not completely understood. Here, we demonstrated that S. pn-secreted H2O2 caused mitochondrial damage and severe histopathological damage in mouse lung tissue. Additionally, S. pn-secreted H2O2 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 H2O2-inducing IFN-I expression in response to mtDNA damaged by S. pn-secreted H2O2. In conclusion, our study demonstrated that H2O2 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.
Insights
Streptococcus pneumoniae (S. pn)-secreted hydrogen peroxide (H2O2) damages mitochondria and host lung tissue. This damage leads to mitochondrial DNA release and type I interferon production, potentially involving STING signaling.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Streptococcus pneumoniae (S. pn) causes invasive pneumococcal diseases and produces hydrogen peroxide (H2O2).
- The precise impact of S. pn-secreted H2O2 on host immune responses remains unclear.
Purpose of the Study:
- To investigate the effects of S. pn-secreted H2O2 on host immune processes, specifically mitochondrial damage and interferon production.
- To elucidate the role of mitochondrial DNA (mtDNA) and STING signaling in the host response to S. pn infection.
Main Methods:
- Mice lung tissue was analyzed for histopathological damage following S. pn infection.
- Mitochondrial damage, mtDNA oxidation, and mtDNA content reduction in alveolar epithelial cells were assessed.
- Type I interferon (IFN-I) expression and the involvement of STING signaling were investigated.
Main Results:
- S. pn-secreted H2O2 induced significant mitochondrial and histopathological damage in mouse lungs.
- Oxidative damage and reduction in mtDNA content were observed in alveolar epithelial cells, leading to mtDNA leakage.
- mtDNA leakage triggered type I interferon (IFN-I) expression, with STING signaling likely playing a role.
Conclusions:
- S. pn-secreted H2O2 causes mitochondrial damage, leading to mtDNA release and subsequent IFN-I production in alveolar epithelial cells.
- STING signaling may be a critical component in the host's IFN-I response to S. pn-induced mitochondrial damage.
- This study reveals a novel mechanism of mitochondrial damage by S. pn that potentiates the IFN-I cascade during infection.
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