An Innate Checkpoint Determines Immune Dysregulation and Immunopathology during Pulmonary Murine Coronavirus Infection.

Grabherr, Sarah; Waltenspühl, Alexandra; Büchler, Lorina; Lütge, Mechthild; Cheng, Hung-Wei; Caviezel-Firner, Sonja; Ludewig, Burkhard; Krebs, Philippe; Pikor, Natalia B (2023). An Innate Checkpoint Determines Immune Dysregulation and Immunopathology during Pulmonary Murine Coronavirus Infection. Journal of immunology, 210(6), pp. 774-785. American Association of Immunologists 10.4049/jimmunol.2200533

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Hallmarks of life-threatening, coronavirus-induced disease include dysregulated antiviral immunity and immunopathological tissue injury. Nevertheless, the sampling of symptomatic patients overlooks the initial inflammatory sequela culminating in severe coronavirus-induced disease, leaving a fundamental gap in our understanding of the early mechanisms regulating anticoronavirus immunity and preservation of tissue integrity. In this study, we delineate the innate regulators controlling pulmonary infection using a natural mouse coronavirus. Within hours of infection, the cellular landscape of the lung was transcriptionally remodeled altering host metabolism, protein synthesis, and macrophage maturation. Genetic perturbation revealed that these transcriptional programs were type I IFN dependent and critically controlled both host cell survival and viral spread. Unrestricted viral replication overshooting protective IFN responses culminated in increased IL-1β and alarmin production and triggered compensatory neutrophilia, interstitial inflammation, and vascular injury. Thus, type I IFNs critically regulate early viral burden, which serves as an innate checkpoint determining the trajectory of coronavirus dissemination and immunopathology.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Krebs, Philippe

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1550-6606

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Pubmed Import

Date Deposited:

01 Feb 2023 09:46

Last Modified:

08 Mar 2023 00:15

Publisher DOI:

10.4049/jimmunol.2200533

PubMed ID:

36715496

BORIS DOI:

10.48350/178129

URI:

https://boris.unibe.ch/id/eprint/178129

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