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

cris.virtual.author-orcid0000-0003-4918-6654
cris.virtualsource.author-orcid9c30bdbd-ec75-42c3-9363-ef07941385d9
dc.contributor.authorGrabherr, Sarah
dc.contributor.authorWaltenspühl, Alexandra
dc.contributor.authorBüchler, Lorina
dc.contributor.authorLütge, Mechthild
dc.contributor.authorCheng, Hung-Wei
dc.contributor.authorCaviezel-Firner, Sonja
dc.contributor.authorLudewig, Burkhard
dc.contributor.authorKrebs, Philippe
dc.contributor.authorPikor, Natalia B
dc.date.accessioned2024-10-15T09:39:51Z
dc.date.available2024-10-15T09:39:51Z
dc.date.issued2023-03-15
dc.description.abstractHallmarks 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.
dc.description.numberOfPages12
dc.description.sponsorshipInstitut für Gewebemedizin und Pathologie
dc.identifier.doi10.48350/178129
dc.identifier.pmid36715496
dc.identifier.publisherDOI10.4049/jimmunol.2200533
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/121096
dc.language.isoen
dc.publisherAmerican Association of Immunologists
dc.relation.ispartofJournal of immunology
dc.relation.issn1550-6606
dc.relation.organizationDCD5A442BF89E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C252E17DE0405C82790C4DE2
dc.subject.ddc500 - Science::570 - Life sciences; biology
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.titleAn Innate Checkpoint Determines Immune Dysregulation and Immunopathology during Pulmonary Murine Coronavirus Infection.
dc.typearticle
dspace.entity.typePublication
dspace.file.typetext
oaire.citation.endPage785
oaire.citation.issue6
oaire.citation.startPage774
oaire.citation.volume210
oairecerif.author.affiliationInstitut für Gewebemedizin und Pathologie
oairecerif.identifier.urlhttps://journals.aai.org/jimmunol/article/doi/10.4049/jimmunol.2200533/237814/An-Innate-Checkpoint-Determines-Immune
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unibe.date.licenseChanged2023-02-01 13:31:41
unibe.description.ispublishedpub
unibe.eprints.legacyId178129
unibe.refereedTRUE
unibe.subtype.articlejournal

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