Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection

Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection

Abstract Inflammation-induced thrombosis is a common consequence of bacterial infections, such as those caused by Salmonella Typhimurium (STm). The presentation of multi-organ thrombosis post-infection that develops and resolves with organ-specific kinetics raises significant challenges for its ther...

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Main Authors: Marisol Perez-Toledo, Nonantzin Beristain-Covarrubias, Jamie Pillaye, Ruby R. Persaud, Edith Marcial-Juarez, Sian E. Jossi, Jessica R. Hitchcock, Areej Alshayea, William M. Channell, Niek T. J. Wiersma, Rachel E. Lamerton, Dean P. Kavanagh, Agostina Carestia, William G. Horsnell, Ian R. Henderson, Nigel Mackman, Andrew R. Clark, Craig N. Jenne, Julie Rayes, Steve P. Watson, Adam F. Cunningham
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57466-6
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Summary:Abstract Inflammation-induced thrombosis is a common consequence of bacterial infections, such as those caused by Salmonella Typhimurium (STm). The presentation of multi-organ thrombosis post-infection that develops and resolves with organ-specific kinetics raises significant challenges for its therapeutic control. Here, we identify specific inflammatory events driving thrombosis in the spleens and livers of STm-infected mice. IFN-γ or platelet expression of C-type lectin-like receptor CLEC-2, key drivers of thrombosis in liver, are dispensable for thrombosis in the spleen. Platelets, monocytes, and neutrophils are identified as core constituents of thrombi in both organs. Depleting either neutrophils or monocytic cells abrogates thrombus formation. Neutrophils and monocytes secrete TNF and blocking TNF diminishes both thrombosis and inflammation, which correlates with reduced endothelial expression of E-selectin and leukocyte infiltration. Moreover, inhibiting tissue factor and P-selectin glycoprotein ligand-1 pathways impairs thrombosis in both spleen and liver. Therefore, we identify organ-specific, and shared mechanisms driving thrombosis within a single infection. This may inform on tailoring treatments towards infection-induced inflammation, and single- or multi-organ thrombosis, based on the clinical need.
ISSN:2041-1723

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