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Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity

ABSTRACT: Immune system dysfunction is paramount in Coronavirus disease 2019 (COVID-19) severity and fatality rate. MAIT cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts of 208 patients at various stages of disease activity. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with other innate cell activation; pro-inflammatory cytokines, notably IL-18; and with the severity and mortality of SARS-CoV-2 infection. We also identified a monocyte/macrophage Interferon-a-IL-18 cytokine shift and the ability of infected macrophages to induce cytotoxicity of MAIT cells in an MR1-dependent manner. Together our results suggest that altered MAIT cell functions due to IFN-a-IL-18 imbalance contribute to disease severity and their therapeutic manipulation might prevent deleterious inflammation in COVID-19 aggravation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164386 | GEO | 2021/01/08

REPOSITORIES: GEO

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