Mice Lacking the Type I Interferon Receptor Are Resistant to Listeria monocytogenes

Abstract

Listeria monocytogenes is a facultative intracellular pathogen that induces a cytosolic signaling cascade resulting in expression of interferon (IFN)-β. Although type I IFNs are critical in viral defense, their role in immunity to bacterial pathogens is much less clear. In this study, we addressed the role of type I IFNs by examining the infection of L. monocytogenes in BALB/c mice lacking the type I IFN receptor (IFN-α/βR^−/−). During the first 24 h of infection in vivo, IFN-α/βR^−/− and wild-type mice were similar in terms of L. monocytogenes survival. In addition, the intracellular fate of L. monocytogenes in macrophages cultured from IFN-α/βR^−/− and wild-type mice was indistinguishable. However, by 72 h after inoculation in vivo, IFN-α/βR^−/− mice were ∼1,000-fold more resistant to a high dose L. monocytogenes infection. Resistance was correlated with elevated levels of interleukin 12p70 in the blood and increased numbers of CD11b⁺ macrophages producing tumor necrosis factor α in the spleen of IFN-α/βR^−/− mice. The results of this study suggest that L. monocytogenes might be exploiting an innate antiviral response to promote its pathogenesis.