期刊
MICROBIOLOGICAL RESEARCH
卷 275, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.micres.2023.127460
关键词
Pyroptosis; Inflammasome; Macrophage; Salmonella; Coagulation; DIC
类别
Inflammasome activation is crucial in defending against bacterial infection. In this study, we discovered that inflammasome activation plays a critical role in the pathogenesis of Salmonella systemic infection. Deficiency of caspase-1 or gasdermin-D prolonged survival, reduced proinflammatory cytokine concentrations, and protected against coagulopathy during Salmonella infection. The activation of NAIP/NLRC4 inflammasome and SPI1 was found to trigger Salmonella-induced coagulopathy, while the caspase-11/NLRP3 pathway was also involved.
Inflammasome activation is a critical defense mechanism against bacterial infection. Previous studies suggest that inflammasome activation protects against Salmonella oral infection. Here we find inflammasome activation plays a critical role in the pathogenesis of Salmonella systemic infection. We show that in a systemic infection model by i.p. injection of Salmonella, deficiency of caspase-1 or gasdermin-D prolonged survival time, reduced plasma concentrations of the proinflammatory cytokines IL-1 & beta;, IL-6 and TNF & alpha;. These deficiencies also protected against coagulopathy during Salmonella infection as evidenced by diminished prolongation of prothrombin time and increase in plasma thrombin-antithrombin complex concentrations in the caspase-1 or gasdermin-D deficient mice. Activation of the NAIP/NLRC4 inflammasome by flagellin and/or the components of the SPI1 type 3 secretion system played a critical role in Salmonella-induced coagulopathy. In the absence of flagellin and SPI1, the Salmonella mutant strain still triggered coagulopathy through the caspase-11/NLRP3 pathway. Our results reveal a previously undisclosed role of the inflammasomes and pyroptosis in the pathogenesis of Salmonella systemic infection.
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