Investigating the mechanisms of thromboinflammation induced by infection

Grant number: 222389/Z/21/Z

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2023
  • Known Financial Commitments (USD)

    $0
  • Funder

    Wellcome Trust
  • Principal Investigator

    Miss. Rachel Lamerton
  • Research Location

    United Kingdom
  • Lead Research Institution

    University of Birmingham
  • Research Priority Alignment

    N/A
  • Research Category

    Clinical characterisation and management

  • Research Subcategory

    Disease pathogenesis

  • Special Interest Tags

    N/A

  • Study Type

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

Thrombosis is estimated to contribute to 25% of deaths worldwide, yet our understanding of the mechanisms behind thrombus formation and related inflammation remain poor. This so-called thromboinflammation can occur as a result of severe infection, for example in sepsis and severe COVID-19. We aim to probe the lifecycle of the thrombus, and understand why it differs between different organs. To do this, we will use the well-established mouse models of Salmonella infection to study the composition of thrombi in different organs. We also aim to investigate the response of human platelets (the main component of many thrombi) to different strains of Salmonella, allowing identification of host and bacterial-specific factors that are affecting the thrombotic response after infection. This research will help further our understanding of the mechanisms behind the dysregulated inflammatory processes that occur upon infection, including during COVID-19, that can lead to fatal consequences.

Publicationslinked via Europe PMC

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

Platelet aggregation responses to <i>Salmonella</i> Typhimurium are determined by host anti-<i>Salmonella</i> antibody levels.

Vancomycin impairs macrophage fungal killing by disrupting mitochondrial morphology and function

<i>Salmonella</i> infection induces the reorganization of follicular dendritic cell networks concomitant with the failure to generate germinal centers.

SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation.

In vitro, classical complement activation differs by disease severity and between SARS-CoV-2 antigens