Intestinal IL-1β Plays a Role in Protecting against SARS-CoV-2 Infection.

Autor:	Lücke J; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Heinrich F; Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Malsy J; I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Leibniz Institute of Virology, Hamburg, Germany.; German Center for Infection Research, Hamburg-Lubeck-Borstel-Riems, Germany., Meins N; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schnell J; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Böttcher M; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Nawrocki M; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Zhang T; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Bertram F; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sabihi M; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kempski J; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Blankenburg T; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Duprée A; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Reeh M; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Wolter S; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Mann O; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Izbicki JR; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lohse AW; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Gagliani N; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lütgehetmann M; Institute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Bunders MJ; Leibniz Institute of Virology, Hamburg, Germany.; III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Altfeld M; Leibniz Institute of Virology, Hamburg, Germany., Sauter G; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Giannou AD; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Krasemann S; Institute for Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Ondruschka B; Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Huber S; Section of Molecular Immunology and Gastroenterology, I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; I Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2023 Sep 15; Vol. 211 (6), pp. 1052-1061.
DOI:	10.4049/jimmunol.2200844
Abstrakt:	The intestine is constantly balancing the maintenance of a homeostatic microbiome and the protection of the host against pathogens such as viruses. Many cytokines mediate protective inflammatory responses in the intestine, among them IL-1β. IL-1β is a proinflammatory cytokine typically activated upon specific danger signals sensed by the inflammasome. SARS-CoV-2 is capable of infecting multiple organs, including the intestinal tract. Severe cases of COVID-19 were shown to be associated with a dysregulated immune response, and blocking of proinflammatory pathways was demonstrated to improve patient survival. Indeed, anakinra, an Ab against the receptor of IL-1β, has recently been approved to treat patients with severe COVID-19. However, the role of IL-1β during intestinal SARS-CoV-2 infection has not yet been investigated. Here, we analyzed postmortem intestinal and blood samples from patients who died of COVID-19. We demonstrated that high levels of intestinal IL-1β were associated with longer survival time and lower intestinal SARS-CoV-2 RNA loads. Concurrently, type I IFN expression positively correlated with IL-1β levels in the intestine. Using human intestinal organoids, we showed that autocrine IL-1β sustains RNA expression of IFN type I by the intestinal epithelial layer. These results outline a previously unrecognized key role of intestinal IL-1β during SARS-CoV-2 infection. (Copyright © 2023 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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