Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality.

Journal

Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445

Informations de publication

Date de publication:
21 Mar 2024
Historique:
received: 15 01 2024
accepted: 08 03 2024
revised: 04 03 2024
medline: 22 3 2024
pubmed: 22 3 2024
entrez: 22 3 2024
Statut: aheadofprint

Résumé

The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19. Concomitantly with occurrence of cell death and inflammation, FasL expression was significantly increased on inflammatory monocytic macrophages and NK cells in the lungs of MA20-infected mice. Importantly, therapeutic FasL inhibition markedly increased survival of both, young and old MA20-infected mice coincident with substantially reduced cell death and inflammation in their lungs. Intriguingly, FasL was also increased in the bronchoalveolar lavage fluid of critically-ill COVID-19 patients. Together, these results identify FasL as a crucial host factor driving the immuno-pathology that underlies COVID-19 severity and lethality, and imply that patients with severe COVID-19 may significantly benefit from therapeutic inhibition of FasL.

Identifiants

DOI: 10.1038/s41418-024-01278-6 PMID: 38514848
pubmed: 38514848
doi: 10.1038/s41418-024-01278-6
pii: 10.1038/s41418-024-01278-6
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Alexander von Humboldt-Stiftung (Alexander von Humboldt Foundation)
ID : 214342/Z/18/Z
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB1399, Project C06
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB1530-455784452, Project A03
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB1403-414786233
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : PID2019-105451GB-I00
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : PID2020-113963RBI00

Informations de copyright

© 2024. The Author(s).

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Auteurs

Marie-Christine Albert (MC)

Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany.
Cell death, inflammation and immunity laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany.

Iratxe Uranga-Murillo (I)

CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, 28029, Spain.
Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain.
Department of Microbiology, Paediatrics, Radiology and Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, 50009, Spain.

Maykel Arias (M)

CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, 28029, Spain.
Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain.
Department of Microbiology, Paediatrics, Radiology and Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, 50009, Spain.

Diego De Miguel (D)

Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain.
ORCID: 0000-0002-8486-8514

Natacha Peña (N)

Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain.

Antonella Montinaro (A)

Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, WC1E 6DD, UK.
ORCID: 0000-0002-2289-9374

Ana Beatriz Varanda (AB)

Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany.
Cell death, inflammation and immunity laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany.

Sebastian J Theobald (SJ)

Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, 50931, Germany.
Faculty of Medicine and University Hospital of Cologne, Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, 50931, Germany.

Itziar Areso (I)

Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, WC1E 6DD, UK.

Julia Saggau (J)

Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany.
Cell death, inflammation and immunity laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany.
Genome instability, inflammation and cell death laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany.

Manuel Koch (M)

Institue for Dental Research and Oral Musculoskeletal Biology, Faculty of Medicine and University Hospital Cologne, Cologne, 50931, Germany.
ORCID: 0000-0002-2962-7814

Gianmaria Liccardi (G)

Genome instability, inflammation and cell death laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany.
ORCID: 0000-0002-2662-1281

Nieves Peltzer (N)

Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany.
Faculty of Medicine and University Hospital of Cologne, Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany.
Department of Translational Genomics, University of Cologne, Cologne, 50931, Germany.
ORCID: 0000-0002-4134-5852

Jan Rybniker (J)

Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, 50931, Germany.
Faculty of Medicine and University Hospital of Cologne, Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, 50931, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, 50931, Germany.
ORCID: 0000-0001-8351-2690

Ramón Hurtado-Guerrero (R)

Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), University of Zaragoza, Zaragoza, 50018, Spain.
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, 2200, Denmark.
Fundación ARAID, Zaragoza, 50018, Spain.
ORCID: 0000-0002-3122-9401

Pedro Merino (P)

Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), University of Zaragoza, Zaragoza, 50018, Spain.

Marta Monzón (M)

Research Centre for Encephalopaties and Transmissible Emerging Diseases, Institute for Health Research Aragón (IIS), University of Zaragoza, Zaragoza, 50013, Spain.
Department of Human Anatomy and Histology, University of Zaragoza, Zaragoza, 50009, Spain.

Juan J Badiola (JJ)

Research Centre for Encephalopaties and Transmissible Emerging Diseases, Institute for Health Research Aragón (IIS), University of Zaragoza, Zaragoza, 50013, Spain.

Roman Reindl-Schwaighofer (R)

Department of Medicine III, Medical University of Vienna, Vienna, 1090, Austria.

Rebeca Sanz-Pamplona (R)

Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain.
Fundación ARAID, Zaragoza, 50018, Spain.
CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, 28029, Spain.

Alberto Cebollada-Solanas (A)

Aragon Biomedical Research Center (CIBA), Instituto Aragonés de Ciencias de la Salud (IACS), Unidad de Biocomputación, Zaragoza, 50018, Spain.

Zsolt Megyesfalvi (Z)

Deparment of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria.
Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, 1122, Hungary.
National Koranyi Institute of Pulmonology, Budapest, 1121, Hungary.

Balazs Dome (B)

Deparment of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria.
Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, 1122, Hungary.
National Koranyi Institute of Pulmonology, Budapest, 1121, Hungary.
Department of Translational Medicine, Lund University, Lund, SE-22100, Sweden.

Maria Secrier (M)

UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, WC1E 6BT, United Kingdom.

Boris Hartmann (B)

Virology Group, Institute for Veterinary Disease Control at AGES, Moedling, 2340, Austria.

Michael Bergmann (M)

Div. of Visceral Surgery, Dept. of General Surgery, Comprehensive Cancer Centre, Medical University of Vienna, Vienna, 1090, Austria.
ORCID: 0000-0001-8529-1166

Julián Pardo (J)

CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, 28029, Spain.
Aragón Health Research Institute (IIS Aragón), San Juan Bosco 13, Zaragoza, 50009, Spain.
Department of Microbiology, Paediatrics, Radiology and Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, 50009, Spain.
ORCID: 0000-0003-0154-0730

Henning Walczak (H)

Cell death, inflammation and immunity laboratory, CECAD Cluster of Excellence, University of Cologne, Cologne, 50931, Germany. h.walczak@uni-koeln.de.
Cell death, inflammation and immunity laboratory, Institute of Biochemistry I, Centre for Biochemistry, Faculty of Medicine, University of Cologne, Cologne, 50931, Germany. h.walczak@uni-koeln.de.
Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, WC1E 6DD, UK. h.walczak@uni-koeln.de.
ORCID: 0000-0002-6312-4591

Classifications MeSH