PRJNA690513: Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity
概要: 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
项目整体设计: MAIT cells single cell analysis from uninfected SARS-CoV-2 patients (n=4) and infected severe cases infected SARS-CoV-patients (n=4). No replicates
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MAIT cells defined as CD3+CD4–TCRgd-CD161hiVa7.2+Tetramer MR1+ were flow-sorted. Single-cell Gel Bead-In-EMulsions (GEMs) were generated using a Chromium Controller instrument (10x Genomics) |
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Sequencing libraries were prepared using Chromium Single Cell 3’ Reagent Kits (10x Genomics) |
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Poly(A)+ RNA |
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ILLUMINA |
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Illumina NextSeq 500 |
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Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity.
Nature immunology . 2021-02-02 [PMID:
33531712]
