Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity.

Autor: Smith N; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Possémé C; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Bondet V; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Sugrue J; School of Biochemistry and Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Townsend L; Discipline of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.; Department of Infectious Diseases, St James's Hospital, Dublin, Ireland., Charbit B; Institut Pasteur, Université Paris Cité, CBUTechS, Center for Translational Research, Paris, France., Rouilly V; Datactix, Bordeaux, France., Saint-André V; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France.; Department of Computational Biology, Université Paris Cité, Bioinformatics and Biostatistics HUB, Institut Pasteur, Paris, France., Dott T; Institut Pasteur, Université Paris Cité, CBUTechS, Center for Translational Research, Paris, France., Pozo AR; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Yatim N; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France., Schwartz O; Department of Virology, Virus and Immunity Unit, Institut Pasteur, Paris, France., Cervantes-Gonzalez M; Infectious and Tropical Diseases Department, AP-HP, Hôpital Bichat, Paris, France.; Epidemiology, Biostatistics and Clinical Research Department, AP-HP, Hôpital Bichat, Paris, France.; Université de Paris, INSERM, IAME, UMR 1137, Paris, France., Ghosn J; Infectious and Tropical Diseases Department, AP-HP, Hôpital Bichat, Paris, France.; Université de Paris, INSERM, IAME, UMR 1137, Paris, France., Bastard P; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Université Paris Cité, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Casanova JL; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Université Paris Cité, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Howard Hughes Medical Institute, New York, NY, USA., Szwebel TA; Institut Cochin, APHP, Paris, France., Terrier B; Institut Cochin, APHP, Paris, France., Conlon N; Department of Immunology, St James's Hospital, Dublin, Ireland.; Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin, Ireland., O'Farrelly C; School of Biochemistry and Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.; Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin, Ireland., Cheallaigh CN; Discipline of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.; Department of Infectious Diseases, St James's Hospital, Dublin, Ireland., Bourke NM; Discipline of Medical Gerontology, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland., Duffy D; Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France. darragh.duffy@pasteur.fr.; Institut Pasteur, Université Paris Cité, CBUTechS, Center for Translational Research, Paris, France. darragh.duffy@pasteur.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 25; Vol. 13 (1), pp. 7254. Date of Electronic Publication: 2022 Nov 25.
DOI: 10.1038/s41467-022-34895-1
Abstrakt: Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported reduced type I interferon in severe COVID-19 patients preceded clinical worsening. Further studies identified genetic mutations in loci of the TLR3- or TLR7-dependent interferon-I pathways, or neutralizing interferon-I autoantibodies as risk factors for development of COVID-19 pneumonia. Here we show in patient cohorts with different severities of COVID-19, that baseline plasma interferon α measures differ according to the immunoassay used, timing of sampling, the interferon α subtype measured, and the presence of autoantibodies. We also show a consistently reduced induction of interferon-I proteins in hospitalized COVID-19 patients upon immune stimulation, that is not associated with detectable neutralizing autoantibodies against interferon α or interferon ω. Intracellular proteomic analysis shows increased monocyte numbers in hospitalized COVID-19 patients but impaired interferon-I response after stimulation. We confirm this by ex vivo whole blood stimulation with interferon-I which induces transcriptomic responses associated with inflammation in hospitalized COVID-19 patients, that is not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to interferon-I based treatments in late stage COVID-19, despite the importance of interferon-I in early acute infection and may guide alternative therapeutic strategies.
(© 2022. The Author(s).)
Databáze: MEDLINE
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