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

Kimia T Maleki; Johanna Tauriainen; Marina García; Priscilla F Kerkman; Wanda Christ; Joana Dias; Julia Wigren Byström; Edwin Leeansyah; Mattias N Forsell; Hans-Gustaf Ljunggren; Clas Ahlm; Niklas K Björkström; Johan K Sandberg; Jonas Klingström

doi:10.1016/j.xcrm.2021.100220

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.

Authors

Kimia T Maleki¹, Johanna Tauriainen¹, Marina García¹, Priscilla F Kerkman^{2

3}, Wanda Christ¹, Joana Dias¹, Julia Wigren Byström², Edwin Leeansyah^{1

4

5}, Mattias N Forsell², Hans-Gustaf Ljunggren¹, Clas Ahlm², Niklas K Björkström¹, Johan K Sandberg¹, Jonas Klingström¹

Affiliations

¹ Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
² Department of Clinical Microbiology, Division of Infection & Immunology, Umeå University, Umeå, Sweden.
³ Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁴ Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, China.
⁵ Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore.

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