Interferon-γ promotes monocyte-mediated lung injury during influenza infection
Department
Research
Document Type
Article
Publication Title
Cell Reports
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.
First Page
110456
DOI
10.1016/j.celrep.2022.110456
Volume
38
Issue
9
Publication Date
3-1-2022
PubMed ID
35235782
Recommended Citation
Schmit, T., Guo, K., & Pichichero, M. E. (2022). Interferon-γ promotes monocyte-mediated lung injury during influenza infection. Cell Reports, 38 (9), 110456. https://doi.org/10.1016/j.celrep.2022.110456
Comments
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