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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Immunol 2021 ; 22 (3): 322-335 Nephropedia Template TP
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Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity #MMPMID33531712
Nat Immunol 2021[Mar]; 22 (3): 322-335 PMID33531712show ga
Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (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 totaling 208 patients with various stages of disease. 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 the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-alpha-IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-alpha-IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation.
|Adult[MESH]
|Aged[MESH]
|Aged, 80 and over[MESH]
|Animals[MESH]
|Bronchoalveolar Lavage[MESH]
|COVID-19/*immunology[MESH]
|Case-Control Studies[MESH]
|Chlorocebus aethiops[MESH]
|Cohort Studies[MESH]
|Female[MESH]
|France[MESH]
|Humans[MESH]
|Immunophenotyping[MESH]
|Interferon-alpha/*immunology[MESH]
|Interleukin-10/immunology[MESH]
|Interleukin-15/immunology[MESH]
|Interleukin-18/*immunology[MESH]
|Interleukin-1beta/immunology[MESH]
|Interleukin-6/immunology[MESH]
|Interleukin-8/immunology[MESH]
|Macrophages/*immunology[MESH]
|Male[MESH]
|Middle Aged[MESH]
|Monocytes/*immunology[MESH]
|Mucosal-Associated Invariant T Cells/*immunology[MESH]