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

TY - JOUR

T1 - Intestinal IL-1β Plays a Role in Protecting against SARS-CoV-2 Infection

AU - Lücke, Jöran

AU - Heinrich, Fabian

AU - Malsy, Jakob

AU - Meins, Nicholas

AU - Schnell, Josa

AU - Böttcher, Marius

AU - Nawrocki, Mikolaj

AU - Zhang, Tao

AU - Bertram, Franziska

AU - Sabihi, Morsal

AU - Kempski, Jan

AU - Blankenburg, Tom

AU - Duprée, Anna

AU - Reeh, Matthias

AU - Wolter, Stefan

AU - Mann, Oliver

AU - Izbicki, Jakob R

AU - Lohse, Ansgar W

AU - Gagliani, Nicola

AU - Lütgehetmann, Marc

AU - Bunders, Madeleine J

AU - Altfeld, Marcus

AU - Sauter, Guido

AU - Giannou, Anastasios D

AU - Krasemann, Susanne

AU - Ondruschka, Benjamin

AU - Huber, Samuel

N1 - Copyright © 2023 by The American Association of Immunologists, Inc.

PY - 2023/9/15

Y1 - 2023/9/15

N2 - 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.

AB - 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.

U2 - 10.4049/jimmunol.2200844

DO - 10.4049/jimmunol.2200844

M3 - SCORING: Journal article

C2 - 37556130

VL - 211

SP - 1052

EP - 1061

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 6

ER -