| First Author | Schmit T | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 9 | Pages | 110456 |
| PubMed ID | 35235782 | Mgi Jnum | J:334664 |
| Mgi Id | MGI:7286259 | Doi | 10.1016/j.celrep.2022.110456 |
| Citation | Schmit T, et al. (2022) Interferon-gamma promotes monocyte-mediated lung injury during influenza infection. Cell Rep 38(9):110456 |
| abstractText | 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-gamma (IFN-gamma)-regulated subset of monocytes, CCR2(+) monocytes, as a driver of lung damage during IAV infection. IFN-gamma regulates the recruitment and inflammatory phenotype of CCR2(+) monocytes, and mice deficient in CCR2 (CCR2(-/-)) or IFN-gamma (IFN-gamma(-/-)) exhibit reduced lung inflammation, pathology, and disease severity. Adoptive transfer of wild-type (WT) (IFN-gammaR1(+/+)) but not IFN-gammaR1(-/-) 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-gamma in IAV-infected lungs. Collectively, our data highlight the requirement of IFN-gamma signaling in the regulation of CCR2(+) monocyte-mediated lung pathology during IAV infection. |
