Salmonella-induced thrombi in mice develop asynchronously in the spleen and liver and are not effective bacterial traps

Research output: Contribution to journalArticle

Authors

  • Nonantzin Beristain-Covarrubias
  • Adriana Flores-langarica
  • Jessica Hitchcock
  • William Channell
  • Lloyd David William King
  • Steve Watson
  • Adam Cunningham

External organisations

  • Institute of Immunology & Immunotherapy, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK

Abstract

Thrombosis is a frequent, life-threatening complication of systemic infection, associated with multiple organ damage. We have previously described a novel mechanism of inflammation-driven thrombosis induced by Salmonella Typhimurium infection of mice. Thrombosis in the liver develops 7 days post-infection persisting after the infection resolves, and is monocytic cell-dependent. Unexpectedly, thrombosis was not prominent in the spleen at this time, despite carrying a similar bacterial burden as the liver. In this study, we show that thrombosis does occur in the spleen but with strikingly accelerated kinetics compared to the liver, being evident by 24 h and resolving rapidly thereafter. The distinct kinetics of thrombosis and bacterial burden provide a test of the hypothesis that thrombi form in healthy vessels to trap or remove bacteria from the circulation, often termed immunothrombosis. Remarkably, despite bacteria being detected throughout infected spleens and livers in the early days of infection, immunohistological analysis of tissue sections show that thrombi contain very low numbers of bacteria. In contrast, bacteria are present throughout platelet aggregates induced by Salmonella in vitro. Therefore, we show that thrombosis develops with organ-specific kinetics and challenge the universality of immunothrombosis as a mechanism to capture bacteria in vivo.

Details

Original languageEnglish
Number of pages8
JournalBlood
Early online date6 Nov 2018
Publication statusE-pub ahead of print - 6 Nov 2018

Keywords

  • immunothrombosis, platelets, monocytes, Inflammation, podoplanin, Salmonella