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

Authors

Ankit Pandeya, University of KentuckyFollow
Yan Zhang, Texas A&M University
Jian Cui, University of KentuckyFollow
Ling Yang, Texas A&M University
Jeffery Li, Texas A&M University
Guoying Zhang, Texas A&M University
Congqing Wu, University of KentuckyFollow
Zhenyu Li, Texas A&M UniversityFollow
Yinan Wei, Texas A&M UniversityFollow

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.

Document Type

Article

Publication Date

10-2023

Notes/Citation Information

0944-5013/© 2023 Elsevier GmbH. This article is made available under the Elsevier license (http://www.elsevier.com/open-access/userlicense/1.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.micres.2023.127460

Funding Information

This work was supported by the National Institutes of Health (R00HL145117 to C.W., R01 HL142640 and GM132443 to Y.W. and Z. L., R01HL146744 to Z.L).

Repository Citation

Pandeya, Ankit; Zhang, Yan; Cui, Jian; Yang, Ling; Li, Jeffery; Zhang, Guoying; Wu, Congqing; Li, Zhenyu; and Wei, Yinan, "Inflammasome activation and pyroptosis mediate coagulopathy and inflammation in Salmonella systemic infection" (2023). Saha Cardiovascular Research Center Faculty Publications. 84.
https://uknowledge.uky.edu/cvrc_facpub/84