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

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-{beta} signaling pathway but does not inhibit IFN-{psi}-mediated cell signaling. The addition of IFN-{beta} 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-{beta}-mediated cell signaling. Finally, we show that the inhibition of the IFN-{beta} 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.