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Published on: May 21, 2018
Apoptotic caspases suppress Mycobacterium bovis-induced IFN-β production in murine macrophage
Yinjuan Song1, Yuhui Dong1, Yi Liao2
1Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Abstract:
Caspases are classified as inflammatory or apoptotic category. Inflammatory caspases participate in inflammasome activation, while apoptotic caspases mediate apoptotic activation. Previous studies have shown that apoptotic caspases prevent the production of IFN-β during apoptosis or virus infection. However, the relationship between apoptotic caspases and IFN-β production during intracellular bacterial infection is still unclear. Here, we investigated the role of apoptotic caspases in IFN-β production induced by Mycobacterium bovis (M. bovis) infection. M. bovis is an intracellular bacterium and belongs to the Mycobacterium tuberculosis complex. M. bovis infection can cause tuberculosis in animals and human beings. In the current study, we found that M. bovis infection triggered mitochondrial stress, which caused the leakage of cytochrome c into the cytoplasm, and in turn, activated the downstream caspase-9 and-3. Furthermore, our results showed that activation of apoptotic caspases reduced IFN-β production during M. bovis infection and vice versa. Confocal microscopy analysis revealed that apoptotic caspases prevented IFN-β production by decreasing p-IRF3 nuclear translocation. Our findings demonstrate that apoptotic caspases negatively regulate the production of IFN-β induced by an intracellular bacterial infection.
Insights
Apoptotic caspases, activated during Mycobacterium bovis infection, hinder the production of interferon-beta (IFN-β). These caspases block IFN-β by preventing key protein movement, revealing a negative regulatory role in bacterial infections.
Area of Science:
- Immunology
- Cellular Biology
- Microbiology
Background:
- Caspases are key regulators of apoptosis and inflammation.
- Apoptotic caspases are known to inhibit interferon-beta (IFN-β) production during viral infections.
- The role of apoptotic caspases in IFN-β production during intracellular bacterial infections remains largely unknown.
Purpose of the Study:
- To investigate the role of apoptotic caspases in IFN-β production following Mycobacterium bovis infection.
- To elucidate the mechanism by which apoptotic caspases affect IFN-β levels during intracellular bacterial pathogenesis.
Main Methods:
- Induction of Mycobacterium bovis infection in relevant cellular models.
- Assessment of caspase activation via mitochondrial stress and cytochrome c release.
- Quantification of IFN-β production.
- Confocal microscopy to analyze p-IRF3 nuclear translocation.
Main Results:
- Mycobacterium bovis infection induced mitochondrial stress, leading to cytochrome c release and activation of caspase-9 and caspase-3.
- Activation of apoptotic caspases was found to inversely correlate with IFN-β production.
- Apoptotic caspases were shown to inhibit IFN-β production by reducing the nuclear translocation of p-IRF3.
Conclusions:
- Apoptotic caspases are activated during Mycobacterium bovis infection.
- Apoptotic caspases negatively regulate IFN-β production in response to intracellular bacterial infection.
- The mechanism involves the inhibition of p-IRF3 nuclear translocation, impacting the innate immune response.
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