Inflammasome Activation and Pyroptosis Mediate Coagulopathy and Inflammation in Salmonella Systemic Infection

Overview

Journal Microbiol Res

Specialties Biotechnology
Environmental Health
Microbiology

Date 2023 Jul 19

PMID 37467711

Authors

Ankit Pandeya

Yan Zhang

Jian Cui

Ling Yang

Jeffery Li

Guoying Zhang

Congqing Wu

Zhenyu Li

Yinan Wei

Affiliations

Soon will be listed here.

Abstract

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-1β, IL-6 and TNFα. 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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