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

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. © 2021 The Author(s)Maleki et al. demonstrate strong activation of mucosal-associated invariant T (MAIT) cells in individuals with hemorrhagic fever with renal syndrome (HFRS) caused by Puumala orthohantavirus. This phenotype is associated with markers of disease severity and is in vitro dependent on type I IFNs. © 2021 The Author(s)