MAIT cell activation is associated with disease severity markers in acute hantavirus infection

Cell Rep Med. 2021 Mar 16;2(3):100220. doi: 10.1016/j.xcrm.2021.100220.

Abstract

Hantaviruses are zoonotic RNA viruses that cause severe acute disease in humans. Infected individuals have strong inflammatory responses that likely cause immunopathology. Here, we studied the response of mucosal-associated invariant T (MAIT) cells in peripheral blood of individuals with hemorrhagic fever with renal syndrome (HFRS) caused by Puumala orthohantavirus, a hantavirus endemic in Europe. We show that MAIT cell levels decrease in the blood during HFRS and that residual MAIT cells are highly activated. This activation correlates with HFRS severity markers. In vitro activation of MAIT cells by hantavirus-exposed antigen-presenting cells is dependent on type I interferons (IFNs) and independent of interleukin-18 (IL-18). These findings highlight the role of type I IFNs in virus-driven MAIT cell activation and suggest a potential role of MAIT cells in the disease pathogenesis of viral infections.

Keywords: IL-6; MAIT cells; Puumala orthohantavirus; T cells; cytokines; endothelial cells; hantavirus; hemorrhagic fever with renal syndrome; monocytes; type I interferons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / virology
  • Biomarkers / metabolism
  • Case-Control Studies
  • Disease Progression
  • Endothelial Cells / immunology
  • Endothelial Cells / virology
  • Female
  • Gene Expression Regulation
  • Hantavirus Infections / genetics
  • Hantavirus Infections / immunology*
  • Hantavirus Infections / pathology
  • Hantavirus Infections / virology
  • Hemorrhagic Fever with Renal Syndrome / genetics
  • Hemorrhagic Fever with Renal Syndrome / immunology*
  • Hemorrhagic Fever with Renal Syndrome / pathology
  • Hemorrhagic Fever with Renal Syndrome / virology
  • Humans
  • Immunophenotyping
  • Interferon Type I / genetics
  • Interferon Type I / immunology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / virology
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / virology
  • Puumala virus / immunology
  • Puumala virus / pathogenicity*
  • Severity of Illness Index

Substances

  • Antibodies, Viral
  • Biomarkers
  • IFNG protein, human
  • IL10 protein, human
  • IL6 protein, human
  • Interferon Type I
  • Interleukin-6
  • Interleukin-10
  • Interferon-gamma