ScholarWorks@중앙대학교

초록

Pyroptosis a lytic form of programmed cell death, is a crucial host defense mechanism against bacterial pathogens. While caspase-mediated pathways are central to pyroptosis, the involvement of apoptotic regulators such as Bak, Bax, and MCL-1 in bacterial infection-induced pyroptosis remains unclear. Here, we investigated how these BCL-2 family proteins modulate pyroptosis induced by Vibrio vulnificus and Salmonella enterica serovar Typhimurium in murine cells. In mouse embryonic fibroblasts (MEFs), both pathogens strongly induced Gbp2 expression and activated caspase-11, whereas activation of caspase-1 occurred only in macrophages, indicating engagement of both non-canonical and canonical pyroptosis pathways. Importantly, Bak-/- and Bax-/- MEFs exhibited significantly reduced Gbp2 upregulation and caspase-11 activation-an effect most pronounced in Bak-deficient cells leading to attenuated pyroptotic cell death. These data suggest that pro-apoptotic proteins, Bak and Bax, act as positive regulators that amplify the Gbp2-caspase-11 axis. Conversely, overexpression of the anti-apoptotic protein MCL-1 had no significant impact on Gbp2 expression, caspase activation, membrane integrity, or LDH release, indicating that pyroptosis proceeds independently of MCL-1 regulation. Collectively, our findings uncover a novel role for Bak and Bax in promoting Gbp2-driven pyroptosis during Gram-negative bacterial infections, while MCL-1 does not impede this process. This work expands our understanding of the crosstalk between apoptotic and pyroptotic pathways in innate immune responses.

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