It is known that host cells can produce type I IFNs (IFN-) 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- 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-R or IFN- died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-R deficiency was marked, with mortality surpassing that seen in IFN-R-deficient mice. Animals lacking both IFN-R and IFN-R displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased production of IFN- was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN- signaling, a marked reduction in macrophage production of IFN-, NO, and TNF- was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN- in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.
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