tetano
Editor, Senior Moderator
Cell Rep
. 2022 Mar 1;38(9):110456.
doi: 10.1016/j.celrep.2022.110456.
Interferon-γ promotes monocyte-mediated lung injury during influenza infection
Taylor Schmit[SUP] 1 [/SUP], Kai Guo[SUP] 2 [/SUP], Jitendra Kumar Tripathi[SUP] 1 [/SUP], Zhihan Wang[SUP] 3 [/SUP], Brett McGregor[SUP] 1 [/SUP], Mitch Klomp[SUP] 1 [/SUP], Ganesh Ambigapathy[SUP] 1 [/SUP], Ramkumar Mathur[SUP] 4 [/SUP], Junguk Hur[SUP] 1 [/SUP], Michael Pichichero[SUP] 5 [/SUP], Jay Kolls[SUP] 6 [/SUP], M Nadeem Khan[SUP] 7 [/SUP]
Affiliations
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[SUP]+[/SUP] monocytes, as a driver of lung damage during IAV infection. IFN-γ regulates the recruitment and inflammatory phenotype of CCR2[SUP]+[/SUP] monocytes, and mice deficient in CCR2 (CCR2[SUP]-/-[/SUP]) or IFN-γ (IFN-γ[SUP]-/-[/SUP]) exhibit reduced lung inflammation, pathology, and disease severity. Adoptive transfer of wild-type (WT) (IFN-γR1[SUP]+/+[/SUP]) but not IFN-γR1[SUP]-/-[/SUP] CCR2[SUP]+[/SUP] monocytes restore the WT-like pathological phenotype of lung damage in IAV-infected CCR2[SUP]-/-[/SUP] mice. CD8[SUP]+[/SUP] 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[SUP]+[/SUP] monocyte-mediated lung pathology during IAV infection.
Keywords: CCR2(+) monocyte; Streptococcus pneumoniae; acute lung injury; influenza; interferon-γ; single-cell RNA sequencing.
. 2022 Mar 1;38(9):110456.
doi: 10.1016/j.celrep.2022.110456.
Interferon-γ promotes monocyte-mediated lung injury during influenza infection
Taylor Schmit[SUP] 1 [/SUP], Kai Guo[SUP] 2 [/SUP], Jitendra Kumar Tripathi[SUP] 1 [/SUP], Zhihan Wang[SUP] 3 [/SUP], Brett McGregor[SUP] 1 [/SUP], Mitch Klomp[SUP] 1 [/SUP], Ganesh Ambigapathy[SUP] 1 [/SUP], Ramkumar Mathur[SUP] 4 [/SUP], Junguk Hur[SUP] 1 [/SUP], Michael Pichichero[SUP] 5 [/SUP], Jay Kolls[SUP] 6 [/SUP], M Nadeem Khan[SUP] 7 [/SUP]
Affiliations
- PMID: 35235782
- DOI: 10.1016/j.celrep.2022.110456
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[SUP]+[/SUP] monocytes, as a driver of lung damage during IAV infection. IFN-γ regulates the recruitment and inflammatory phenotype of CCR2[SUP]+[/SUP] monocytes, and mice deficient in CCR2 (CCR2[SUP]-/-[/SUP]) or IFN-γ (IFN-γ[SUP]-/-[/SUP]) exhibit reduced lung inflammation, pathology, and disease severity. Adoptive transfer of wild-type (WT) (IFN-γR1[SUP]+/+[/SUP]) but not IFN-γR1[SUP]-/-[/SUP] CCR2[SUP]+[/SUP] monocytes restore the WT-like pathological phenotype of lung damage in IAV-infected CCR2[SUP]-/-[/SUP] mice. CD8[SUP]+[/SUP] 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[SUP]+[/SUP] monocyte-mediated lung pathology during IAV infection.
Keywords: CCR2(+) monocyte; Streptococcus pneumoniae; acute lung injury; influenza; interferon-γ; single-cell RNA sequencing.