MAIT cell activation and dynamics associated with COVID-19 disease severity.

Tiphaine Parrot ,Tobias Kammann ,Sara Gredmark‐Russ ,Marcus Buggert ,André Perez‐Potti ,Hans‐Gustaf Ljunggren ,Jonas Klingström ,Niklas K Björkström ,Jean‐Baptiste Gorin ,Lars Eriksson ,Olga Rivera‐Ballesteros ,Soo Aleman ,Andrea Ponzetta ,Elin Folkesson ,Olav Rooyackers ,Kristoffer Strålin ,Takuya Sekine ,Anna Norrby‐Teglund ,Johanna Emgård ,Kimia T Maleki ,Johan K Sandberg

doi:10.1126/sciimmunol.abe1670

Tiphaine Parrot , Tobias Kammann + Show 19 more

Open Access

https://doi.org/10.1126/sciimmunol.abe1670

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Abstract

Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69high and CXCR3low immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.

Highlights

Severe acute respiratory syndrome (SARS) coronavirus-2 (SARSCoV-2) causes viral pneumonia and coronavirus disease 2019 (COVID-19), which, in some individuals, progresses to acute respiratory distress syndrome characterized by aggressive inflammatory responses in the lower airways [reviewed in [1]]
Projecting data from healthy donors (HDs), acute patients with moderate (AM), and AS subjects separately revealed a clear difference between patients and controls with severe reduction in the distinct topography defined by the MHC-Ib–related protein 1 (MR1)-5-OP-RU tetramer, suggesting loss of Mucosa-associated invariant T (MAIT) cells in COVID-19 (Fig. 1B)
MAIT cells play a significant role in the immune defense against microbial infections in mucosal barriers via T cell receptor (TCR)-mediated recognition of MR1-presented riboflavin metabolites

Summary

Introduction

Severe acute respiratory syndrome (SARS) coronavirus-2 (SARSCoV-2) causes viral pneumonia and coronavirus disease 2019 (COVID-19), which, in some individuals, progresses to acute respiratory distress syndrome characterized by aggressive inflammatory responses in the lower airways [reviewed in [1]]. Severe COVID-19 is due to direct effects of the virus and, in part, to a misdirected host response with complex immune dysregulation of both innate and adaptive immune and inflammatory components [2, 3]. Mucosa-associated invariant T (MAIT) cells represent 1 to 10% of T cells in the circulation, Emerging evidence indicates that MAIT cells are innate-like sensors of viral infection; human MAIT cells are activated in response to several RNA viruses [25, 26], expand during acute stages of HIV-1 infection [27], and may have a protective role in influenza virus infection as deduced from studies in murine models [28]. Our findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis

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