Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria

It is known that host cells can produce type I IFNs (IFN-alpha beta) after exposure to conserved bacterial products, but the functional consequences of such responses on the outcome of bacterial infections are incompletely understood. We show in this study that IFN-alpha beta signaling is crucial for host defenses against different bacteria, including group B streptococci (GBS), pneumococci, and Escherichia coli. In response to GBS challenge, most mice lacking either the IFN-alpha beta R or IFN-beta died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-alpha beta R deficiency was marked, with mortality surpassing that seen in IFN-gamma R-deficient mice. Animals lacking both IFN-alpha beta R and IFN-gamma R displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased procluction of IFN-alpha beta was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN-alpha beta signaling, a marked reduction in macrophage production of IFN-gamma, NO, and TNF-alpha was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN-alpha beta in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections