Legionella pneumophila inhibits type I interferon signaling to avoid cell-intrinsic host cell defense

Infect Immun. 2023 Nov 16;91(11):e0036523. doi: 10.1128/iai.00365-23. Epub 2023 Oct 16.

Abstract

The host type I interferon (IFN) response protects against Legionella pneumophila infections. Other bacterial pathogens inhibit type I IFN-mediated cell signaling; however, the interaction between this signaling pathway and L. pneumophila has not been well described. Here, we demonstrate that L. pneumophila inhibits the IFN-β signaling pathway but does not inhibit IFN-γ-mediated cell signaling. The addition of IFN-β to L. pneumophila-infected macrophages limited bacterial growth independently of NOS2 and reactive nitrogen species. The type IV secretion system of L. pneumophila is required to inhibit IFN-β-mediated cell signaling. Finally, we show that the inhibition of the IFN-β signaling pathway occurs downstream of STAT1 and STAT2 phosphorylation. In conclusion, our findings describe a novel host cell signaling pathway inhibited by L. pneumophila via its type IV secretion system.

Keywords: Legionella pneumophila; immune evasion; interferons; nitric oxide; secretion systems.

MeSH terms

  • Humans
  • Interferon Type I*
  • Interferon-gamma / metabolism
  • Legionella pneumophila* / physiology
  • Legionnaires' Disease*
  • Signal Transduction
  • Type IV Secretion Systems

Substances

  • Type IV Secretion Systems
  • Interferon-gamma
  • Interferon Type I