Interferon-γ promotes monocyte-mediated lung injury during influenza infection.
Cell Rep
; 38(9): 110456, 2022 03 01.
Article
de En
| MEDLINE
| ID: mdl-35235782
ABSTRACT
Influenza A virus (IAV) infection triggers an exuberant host response that promotes acute lung injury. However, the host response factors that promote the development of a pathologic inflammatory response to IAV remain incompletely understood. In this study, we identify an interferon-γ (IFN-γ)-regulated subset of monocytes, CCR2+ monocytes, as a driver of lung damage during IAV infection. IFN-γ regulates the recruitment and inflammatory phenotype of CCR2+ monocytes, and mice deficient in CCR2 (CCR2-/-) or IFN-γ (IFN-γ-/-) exhibit reduced lung inflammation, pathology, and disease severity. Adoptive transfer of wild-type (WT) (IFN-γR1+/+) but not IFN-γR1-/- CCR2+ monocytes restore the WT-like pathological phenotype of lung damage in IAV-infected CCR2-/- mice. CD8+ T cells are the main source of IFN-γ in IAV-infected lungs. Collectively, our data highlight the requirement of IFN-γ signaling in the regulation of CCR2+ monocyte-mediated lung pathology during IAV infection.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Virus de la grippe A
/
Infections à Orthomyxoviridae
/
Grippe humaine
/
Lésion pulmonaire
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Cell Rep
Année:
2022
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique