Lack of IFNγ signaling attenuates spread of influenza A virus in vivo and leads to reduced pathogenesis

Virology. 2019 Jan 2:526:155-164. doi: 10.1016/j.virol.2018.10.017. Epub 2018 Oct 31.

Abstract

IFNγ is a key regulator of inflammatory responses but its role in influenza A virus (IAV) pathogenesis is unclear. Our studies show that infection of mice lacking the IFNγ receptor (IFNγR-/-) at a dose which caused severe disease in wild type 129 Sv/Ev (WT) mice resulted in milder clinical symptoms and significantly lower lung virus titers by 6 days post-infection (dpi). Viral spread was reduced in IFNγR-/- lungs at 2 and 4 dpi. Levels of inflammatory cytokines and chemokines were lower in IFNγR-/- mice at 2 dpi and there was less infiltration of monocyte/macrophage lineage cells than in WT mice. There was no difference in CD4+ and CD8+ T cells and alveolar macrophages in the bronchoalveolar lavage fluid (BALF) at 2 and 4 dpi but by 4 dpi IFNγR-/- mice had significantly higher percentages of neutrophils. Our data strongly suggest that IAV can use the inflammatory response to promote viral spread.

Keywords: Host response; IFNγ; Influenza A virus; Lung inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / metabolism
  • Influenza A virus / pathogenicity*
  • Interferon gamma Receptor
  • Lung / metabolism
  • Lung / pathology
  • Lung / virology
  • Macrophages / immunology
  • Mice
  • Mice, Transgenic
  • Neutrophils / immunology
  • Orthomyxoviridae Infections / metabolism
  • Orthomyxoviridae Infections / physiopathology*
  • Orthomyxoviridae Infections / virology
  • Receptors, Interferon / genetics*
  • Signal Transduction* / genetics
  • Viral Load

Substances

  • Cytokines
  • Receptors, Interferon