Inflammasome activation and pyroptosis mediate coagulopathy and inflammation in Salmonella systemic infection

Ankit Pandeya, Yan Zhang, Jian Cui, Ling Yang, Jeffery Li, Guoying Zhang, Congqing Wu, Zhenyu Li, Yinan Wei

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Article number127460
JournalMicrobiological Research
Volume275
DOIs
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier GmbH

Keywords

  • Coagulation
  • DIC
  • Inflammasome
  • Macrophage
  • Pyroptosis
  • Salmonella

ASJC Scopus subject areas

  • Microbiology

Fingerprint

Dive into the research topics of 'Inflammasome activation and pyroptosis mediate coagulopathy and inflammation in Salmonella systemic infection'. Together they form a unique fingerprint.

Cite this