Maqola

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

Jérôme HadjadjDepartment of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, FranceNader YatimDepartment of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, FranceLaura BarnabeiUniversité de Paris, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, F-75015 Paris, FranceAurélien CorneauSorbonne Université, UMS037, PASS, Plateforme de cytométrie de la Pitié-Salpêtrière CyPS, F-75013 Paris, FranceJérémy BoussierInstitut Pasteur, Laboratory of Dendritic Cell Immunobiology, INSERM U1223, Department of Immunology, F-75015 Paris, FranceNikaïa SmithInstitut Pasteur, Laboratory of Dendritic Cell Immunobiology, INSERM U1223, Department of Immunology, F-75015 Paris, FranceHélène PéréService de Microbiologie, AP-HP, APHP-CUP, Hôpital Européen Georges Pompidou, F-75015 Paris, FranceBruno CharbitInstitut Pasteur, Cytometry and Biomarkers UTechS, CRT, F-75015 Paris, FranceVincent BondetInstitut Pasteur, Laboratory of Dendritic Cell Immunobiology, INSERM U1223, Department of Immunology, F-75015 Paris, FranceCamille Chenevier‐GobeauxDepartment of Automated Diagnostic Biology, Hôpital Cochin, APHP, APHP-CUP, F-75014 Paris, FrancePaul BreillatDepartment of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, FranceNicolas CarlierDepartment of Pulmonology, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, FranceR. GauzitEquipe Mobile d’Infectiologie, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, FranceCaroline MorbieuDepartment of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, FranceFrédéric PèneService de Médecine Intensive et Réanimation, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, FranceNathalie MarinService de Médecine Intensive et Réanimation, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, FranceNicolás RocheDepartment of Pulmonology, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, FranceTali‐Anne SzwebelDepartment of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, FranceSarah H. MerklingInstitut Pasteur, Insect-Virus Interactions Unit, UMR 2000, CNRS, Paris, FranceJean‐Marc TréluyerRecherche Clinique et Pharmacologie, AP-HP, APHP-CUP, Hôpitaux Cochin Necker, F-75014 Paris, FranceDavid VeyerService de Microbiologie, AP-HP, APHP-CUP, Hôpital Européen Georges Pompidou, F-75015 Paris, FranceLuc MouthonHôpital CochinCatherine BlancSorbonne Université, UMS037, PASS, Plateforme de cytométrie de la Pitié-Salpêtrière CyPS, F-75013 Paris, FrancePierre‐Louis TharauxUniversité de Paris, INSERM, U970, PARCC, F-75015 Paris, FranceFlore RozenbergService de Virologie, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, FranceAlain FischerCollège de France, Paris, FranceDarragh DuffyInstitut Pasteur, Cytometry and Biomarkers UTechS, CRT, F-75015 Paris, FranceFrédéric Rieux‐LaucatUniversité de Paris, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, F-75015 Paris, FranceSolen KernéisEquipe Mobile d’Infectiologie, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, FranceBenjamin TerrierDepartment of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, France

2020en

ABI

Annotatsiya

Interferons interfere with lung repair Interferons (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), which engage in various antiviral functions. Type I IFNs (IFN-α and IFN-β) are widely expressed and can result in immunopathology during viral infections. By contrast, type III IFN (IFN-λ) responses are primarily restricted to mucosal surfaces and are thought to confer antiviral protection without driving damaging proinflammatory responses. Accordingly, IFN-λ has been proposed as a therapeutic in coronavirus disease 2019 (COVID-19) and other such viral respiratory diseases (see the Perspective by Grajales-Reyes and Colonna). Broggi et al. report that COVID-19 patient morbidity correlates with the high expression of type I and III IFNs in the lung. Furthermore, IFN-λ secreted by dendritic cells in the lungs of mice exposed to synthetic viral RNA causes damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. Similarly, using a mouse model of influenza infection, Major et al. found that IFN signaling (especially IFN-λ) hampers lung repair by inducing p53 and inhibiting epithelial proliferation and differentiation. Complicating this picture, Hadjadj et al. observed that peripheral blood immune cells from severe and critical COVID-19 patients have diminished type I IFN and enhanced proinflammatory interleukin-6– and tumor necrosis factor-α–fueled responses. This suggests that in contrast to local production, systemic production of IFNs may be beneficial. The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections. Science , this issue p. 706 , p. 712 , p. 718 ; see also p. 626

Hali tarjima qilinmagan

Identifikatorlar

DOI: 10.1126/science.abc6027

Iqtiboslar va manbalar

3 ta iqtibos0 ta foydalanilgan manba

Koʻrsatkichlar — AkademScholar