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Nature immunology
03, 2021;22 (3): 322-335.

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

Héloïse Flament, Matthieu Rouland, Lucie Beaudoin, Amine Toubal, Léo Bertrand, Samuel Lebourgeois, Camille Rousseau, Pauline Soulard, Zouriatou Gouda, Lucie Cagninacci, Antoine C Monteiro, Margarita Hurtado-Nedelec, Sandrine Luce, Karine Bailly, Muriel Andrieu, Benjamin Saintpierre, Franck Letourneur, Youenn Jouan, Mustapha Si-Tahar, Thomas Baranek, Christophe Paget, Christian Boitard, Anaïs Vallet-Pichard, Jean-François Gautier, Nadine Ajzenberg, Benjamin Terrier, Frédéric Pène, Jade Ghosn, Xavier Lescure, Yazdan Yazdanpanah, Benoit Visseaux, Diane Descamps, Jean-François Timsit, Renato C Monteiro, Agnès Lehuen
Author Information
  1. Héloïse Flament: Laboratory of Immunological Dysfunction, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat-Claude Bernard University Hospital, Paris, France.
  2. Matthieu Rouland: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France. ORCID
  3. Lucie Beaudoin: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  4. Amine Toubal: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France. ORCID
  5. Léo Bertrand: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France. ORCID
  6. Samuel Lebourgeois: Department of Virology, AP-HP, Bichat-Claude Bernard University Hospital, Paris, France.
  7. Camille Rousseau: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  8. Pauline Soulard: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  9. Zouriatou Gouda: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  10. Lucie Cagninacci: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  11. Antoine C Monteiro: Department of Virology, AP-HP, Bichat-Claude Bernard University Hospital, Paris, France.
  12. Margarita Hurtado-Nedelec: Laboratory of Immunological Dysfunction, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat-Claude Bernard University Hospital, Paris, France. ORCID
  13. Sandrine Luce: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France. ORCID
  14. Karine Bailly: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  15. Muriel Andrieu: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  16. Benjamin Saintpierre: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  17. Franck Letourneur: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  18. Youenn Jouan: Université de Tours, Inserm, Centre d'Etude des Pathologies Respiratoires UMR 1100, Tours, France.
  19. Mustapha Si-Tahar: Université de Tours, Inserm, Centre d'Etude des Pathologies Respiratoires UMR 1100, Tours, France.
  20. Thomas Baranek: Université de Tours, Inserm, Centre d'Etude des Pathologies Respiratoires UMR 1100, Tours, France.
  21. Christophe Paget: Université de Tours, Inserm, Centre d'Etude des Pathologies Respiratoires UMR 1100, Tours, France.
  22. Christian Boitard: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  23. Anaïs Vallet-Pichard: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  24. Jean-François Gautier: Department of Diabetes and Endocrinology, AP-HP, Lariboisière Hospital, Paris, France.
  25. Nadine Ajzenberg: Department of Hematology, AP-HP, Bichat-Claude Bernard University Hospital, Paris, France.
  26. Benjamin Terrier: Department of Internal Medicine, AP-HP, Cochin University Hospital, Paris, France.
  27. Frédéric Pène: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.
  28. Jade Ghosn: Université de Paris, Infections Antimicrobials Modelling Evolution UMR 1137, Paris, France.
  29. Xavier Lescure: Université de Paris, Infections Antimicrobials Modelling Evolution UMR 1137, Paris, France.
  30. Yazdan Yazdanpanah: Université de Paris, Infections Antimicrobials Modelling Evolution UMR 1137, Paris, France.
  31. Benoit Visseaux: Department of Virology, AP-HP, Bichat-Claude Bernard University Hospital, Paris, France.
  32. Diane Descamps: Department of Virology, AP-HP, Bichat-Claude Bernard University Hospital, Paris, France.
  33. Jean-François Timsit: Université de Paris, Infections Antimicrobials Modelling Evolution UMR 1137, Paris, France.
  34. Renato C Monteiro: Laboratory of Immunological Dysfunction, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat-Claude Bernard University Hospital, Paris, France. ORCID
  35. Agnès Lehuen: Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France. agnes.lehuen@inserm.fr. ORCID
PMID: 33531712 DOI: 10.1038/s41590-021-00870-z

Abstract

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)-α-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-α-IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation.

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Grants

  1. ANR-11-IDEX-0005-02/Agence Nationale de la Recherche (French National Research Agency)
  2. ANR-17-CE14-0002-01/Agence Nationale de la Recherche (French National Research Agency)
  3. ANR-19-CE14-0020/Agence Nationale de la Recherche (French National Research Agency)
  4. ANR-17-RHUS-009/Agence Nationale de la Recherche (French National Research Agency)
  5. EQU201903007779/Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
  6. EQU201903007816/Fondation pour la Recherche Médicale (Foundation for Medical Research in France)

MeSH Term

Adult
Aged
Aged, 80 and over
Animals
Bronchoalveolar Lavage
COVID-19
Case-Control Studies
Chlorocebus aethiops
Cohort Studies
Female
France
Humans
Immunophenotyping
Interferon-alpha
Interleukin-10
Interleukin-15
Interleukin-18
Interleukin-1beta
Interleukin-6
Interleukin-8
Macrophages
Male
Middle Aged
Monocytes
Mucosal-Associated Invariant T Cells
RNA-Seq
SARS-CoV-2
Severity of Illness Index
Single-Cell Analysis
Vero Cells
Young Adult

Chemicals

Interferon-alpha
Interleukin-15
Interleukin-18
Interleukin-1beta
Interleukin-6
Interleukin-8
Interleukin-10
Journal Article Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000440 (Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity)

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