Antimicrobial immunity impedes CNS vascular repair following brain injury.
Animals
Anti-Infective Agents
/ immunology
Blood-Brain Barrier
/ immunology
Brain
/ immunology
Brain Injuries, Traumatic
/ immunology
Central Nervous System
/ immunology
Disease Models, Animal
Female
Immunity, Innate
/ immunology
Interferon Type I
/ immunology
Male
Mice
Mice, Inbred C57BL
Signal Transduction
/ immunology
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
15
12
2020
accepted:
27
07
2021
pubmed:
25
9
2021
medline:
13
10
2021
entrez:
24
9
2021
Statut:
ppublish
Résumé
Traumatic brain injury (TBI) and cerebrovascular injury are leading causes of disability and mortality worldwide. Systemic infections often accompany these disorders and can worsen outcomes. Recovery after brain injury depends on innate immunity, but the effect of infections on this process is not well understood. Here, we demonstrate that systemically introduced microorganisms and microbial products interfered with meningeal vascular repair after TBI in a type I interferon (IFN-I)-dependent manner, with sequential infections promoting chronic disrepair. Mechanistically, we discovered that MDA5-dependent detection of an arenavirus encountered after TBI disrupted pro-angiogenic myeloid cell programming via induction of IFN-I signaling. Systemic viral infection similarly blocked restorative angiogenesis in the brain parenchyma after intracranial hemorrhage, leading to chronic IFN-I signaling, blood-brain barrier leakage and a failure to restore cognitive-motor function. Our findings reveal a common immunological mechanism by which systemic infections deviate reparative programming after central nervous system injury and offer a new therapeutic target to improve recovery.
Identifiants
pubmed: 34556874
doi: 10.1038/s41590-021-01012-1
pii: 10.1038/s41590-021-01012-1
pmc: PMC8488012
mid: NIHMS1728548
doi:
Substances chimiques
Anti-Infective Agents
0
Interferon Type I
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1280-1293Subventions
Organisme : Intramural NIH HHS
ID : ZIA NS003111
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA NS003112
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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