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

被引：157

作者：

Flament, Heloise ^{[1
,2
,3
]}

Rouland, Matthieu ^{[4
]}

Beaudoin, Lucie ^{[4
]}

Toubal, Amine ^{[4
]}

Bertrand, Leo ^{[4
]}

Lebourgeois, Samuel ^{[5
,6
]}

Rousseau, Camille ^{[4
]}

Soulard, Pauline ^{[4
]}

Gouda, Zouriatou ^{[4
]}

Cagninacci, Lucie ^{[4
]}

Monteiro, Antoine C. ^{[5
,6
]}

Hurtado-Nedelec, Margarita ^{[1
,2
,3
]}

Luce, Sandrine ^{[4
]}

Bailly, Karine ^{[4
]}

Andrieu, Muriel ^{[4
]}

Saintpierre, Benjamin ^{[4
]}

Letourneur, Franck ^{[4
]}

Jouan, Youenn ^{[7
,8
]}

Si-Tahar, Mustapha ^{[7
]}

Baranek, Thomas ^{[7
]}

Paget, Christophe ^{[7
]}

Boitard, Christian ^{[4
,9
]}

Vallet-Pichard, Anais ^{[4
,10
]}

Gautier, Jean-Francois ^{[11
]}

Ajzenberg, Nadine ^{[12
,13
]}

Terrier, Benjamin ^{[14
]}

Pene, Frederic ^{[4
,15
]}

Ghosn, Jade ^{[6
,16
]}

Lescure, Xavier ^{[6
,16
]}

Yazdanpanah, Yazdan ^{[6
,16
]}

Visseaux, Benoit ^{[5
,6
]}

Descamps, Diane ^{[5
,6
]}

Timsit, Jean-Francois ^{[6
,17
]}

Monteiro, Renato C. ^{[1
,2
,3
]}

Lehuen, Agnes ^{[4
]}

机构：

[1] Bichat Claude Bernard Univ Hosp, AP HP, Lab Immunol Dysfunct, Paris, France

[2] Univ Paris, Ctr Res Inflammat, INSERM, U1149, Paris, France

[3] CNRS, Inflamex Lab, ERL8252, Paris, France

[4] Univ Paris, Inflamex Lab, Inst Cochin, Inserm,U1016,CNRS,UMR 8104, Paris, France

[5] Bichat Claude Bernard Univ Hosp, AP HP, Dept Virol, Paris, France

[6] Univ Paris, Infect Antimicrobials Modelling Evolut UMR 1137, Paris, France

[7] Univ Tours, Ctr Etud Pathol Resp UMR 1100, INSERM, Tours, Indre & Loire, France

[8] Tours Reg Univ Hosp, Intens Care Med Unit, Tours, France

[9] Cochin Univ Hosp, AP HP, Dept Diabetol, Paris, France

[10] Cochin Univ Hosp, AP HP, Dept Hepatol, Paris, France

[11] Lariboisiere Hosp, AP HP, Dept Diabet & Endocrinol, Paris, France

[12] Bichat Claude Bernard Univ Hosp, AP HP, Dept Hematol, Paris, France

[13] Univ Paris, INSERM, LVTS, Paris, France

[14] Cochin Univ Hosp, AP HP, Dept Internal Med, Paris, France

[15] Cochin Univ Hosp, AP HP, Med Intens Care Unit, Paris, France

[16] Bichat Claude Bernard Univ Hosp, AP HP, Dept Infect & Trop Dis, Paris, France

[17] Bichat Claude Bernard Univ Hosp, AP HP, Med & Infect Dis Intens Care Unit, Paris, France

来源：

NATURE IMMUNOLOGY | 2021年 / 22卷 / 03期

关键词：

INVARIANT T-CELLS; IMMUNITY; TCR;

D O I：

10.1038/s41590-021-00870-z

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Severe COVID-19 is characterized by hyperinflammation, and there is a need for accurate predictive biomarkers of progression. Lehuen et al. demonstrate that patients with severe COVID-19 show a dramatic loss of MAIT cells, and those that do remain are in a highly activated state. 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.

引用

页码：322 / +

页数：31

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