The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.

Autor: Cabrera LE; Viral Zoonosis Research Unit, Medicum, Department of Virology, University of Helsinki, Helsinki, Finland., Jokiranta ST; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.; Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Mäki S; Viral Zoonosis Research Unit, Medicum, Department of Virology, University of Helsinki, Helsinki, Finland., Miettinen S; Viral Zoonosis Research Unit, Medicum, Department of Virology, University of Helsinki, Helsinki, Finland.; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland., Kant R; Viral Zoonosis Research Unit, Medicum, Department of Virology, University of Helsinki, Helsinki, Finland.; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.; Department of Tropical Parasitology, Institute of Maritime and Tropical Medicine, Medical University of Gdansk, Gdynia, Poland., Kareinen L; Viral Zoonosis Research Unit, Medicum, Department of Virology, University of Helsinki, Helsinki, Finland.; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland., Sironen T; Viral Zoonosis Research Unit, Medicum, Department of Virology, University of Helsinki, Helsinki, Finland.; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland., Pietilä JP; Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Meilahti Vaccine Research Center MeVac, Department of Infectious Diseases, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Kantele A; Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Meilahti Vaccine Research Center MeVac, Department of Infectious Diseases, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Kekäläinen E; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.; Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Division of Virology and Immunology, HUSLAB Clinical Microbiology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Lindgren H; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland., Mattila P; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland., Kipar A; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.; Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.; Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom., Vapalahti O; Viral Zoonosis Research Unit, Medicum, Department of Virology, University of Helsinki, Helsinki, Finland.; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.; Division of Virology and Immunology, HUSLAB Clinical Microbiology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Strandin T; Viral Zoonosis Research Unit, Medicum, Department of Virology, University of Helsinki, Helsinki, Finland.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Aug 22; Vol. 20 (8), pp. e1012368. Date of Electronic Publication: 2024 Aug 22 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012368
Abstrakt: The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes. These findings suggest a potential role for neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Cabrera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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