Interferon-γ promotes monocyte-mediated lung injury during influenza infection

Cell Rep. 2022 Mar 1;38(9):110456. 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+ 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.

Keywords: CCR2(+) monocyte; Streptococcus pneumoniae; acute lung injury; influenza; interferon-γ; single-cell RNA sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Humans
  • Influenza A virus*
  • Influenza, Human*
  • Interferon-gamma
  • Lung
  • Lung Injury*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes
  • Orthomyxoviridae Infections* / complications

Substances

  • Interferon-gamma