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.

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

“…On the contrary, induction of type I interferons by L. monocytogenes is beneficial to the bacteria. In the absence of type I interferon signaling, L. monocytogenes cannot reach as high titers in mice and mice with elevated levels of type I interferons have greater bacterial loads [28][29][30]. This suggests that L. monocytogenes induces type I interferon to its benefit to either directly enhance its growth, or more likely, downmodulate a part of the immune response that plays an important role in controlling bacterial growth.…”

IL-12 and Type-I IFN Synergize for IFN-γ Production by CD4 T Cells, Whereas Neither Are Required for IFN-γ Production by CD8 T Cells afterListeria monocytogenesInfection

“…As a consequence, mice deficient in IFN-IR become highly susceptible to most viral infections. By marked contrast, mice deficient in IFN-IR compared with control mice are more resistant to primary Lm infection (15)(16)(17). A possible mechanistic explanation for these results is that IFN-I produced during Lm infection sensitizes and enhances early lymphocyte apoptosis, which in turn leads to a cascade of events, including the production anti-inflammatory cytokines by the phagocytes, resulting in a more permissive niche for bacterial replication (22).…”

Interfering with Immunity: Detrimental Role of Type I IFNs during Infection

“…infection with the bacteria induces type I IFN expression in mice (52,57), and Ifnar1 2/2 mice are more resistant to infection compared with WT mice (53,58,59). In addition, pretreatment of mice with polyinosinicpolycytidylic acid (poly I:C), an inducer of type I IFNs, increases their susceptibility to L. monocytogenes infection (53).…”

“…Type I IFNs were shown to increase lymphocyte apoptosis (53,59,60), enhance macrophage cell death (61,62), antagonize IFN-g signaling by downregulating the IFNGR on APCs (63), inhibit neutrophil migration (64), and reduce the production of protective IL-12 and TNF-a (58,59). Together, these findings suggest that the bacteriuminduced type I IFNs can modulate multiple protective mechanisms to impair survival of the infected host.…”