Type I IFN Does Not Promote Susceptibility to Foodborne Listeria monocytogenes

Abstract

Type I IFN (IFNα/β) is thought to enhance growth of the foodborne intracellular pathogen Listeria monocytogenes (Lm) by promoting mechanisms that dampen innate immunity to infection. However, the type I IFN response has been studied primarily using methods that bypass the stomach and, therefore, fail to replicate the natural course of Lm infection. In this study, we compared i.v. and foodborne transmission of Lm in mice lacking the common type I IFN receptor (IFNAR1−/−). Contrary to what was observed using i.v. infection, IFNAR1−/− and wild type mice had similar bacterial burdens in the liver and spleen following foodborne infection. Splenocytes from wild type mice infected intravenously produced significantly more IFNβ than those infected by the foodborne route. Consequently, the immunosuppressive effects of type I IFN signaling, which included T cell death, increased IL-10 secretion, and repression of neutrophil recruitment to the spleen, were all observed following i.v., but not foodborne transmission of Lm. Type I IFN was also previously shown to cause a loss of responsiveness to IFNγ through down-regulation of the receptor IFNGR1 on macrophages and dendritic cells. However, we detected a decrease in surface expression of IFNGR1 even in the absence of IFNα/β signaling, suggesting that in vivo, this infection-induced phenotype is not type I IFN-dependent. These results highlight the importance of using the natural route of infection for studies of host-pathogen interactions and suggest that the detrimental effects of IFNα/β signaling on the innate immune response to Lm may be an artifact of the i.v. infection model.

Type I and III Interferon in the Gut: Tight Balance between Host Protection and Immunopathology

“…Diminished restriction of bacterial growth in the absence of type I IFN signaling resulted in exacerbated hepatic inflammation and damage (65). Different results were obtained by a more recent study using an EGDe derivative strain expressing "murinized" InlA (66). Contrasting systemic infection, which leads to strong type I IFN secretion, oral infection with this strain did not trigger robust type I IFN induction in splenocytes even when comparable bacterial burdens were present in the spleen.…”

Type I Interferons in Bacterial Infections: A Balancing Act

“…Type I IFNs are harmful followed intraperitoneal or intravenous infection with L. monocytogenes but protective in a physiologically more relevant intragastric infection (25–28). In contrast, type I IFN signaling has no impact on the overall outcome of L. monocytogenes infection after ingesting pathogen-contaminated food (30). These observations suggest that type I IFN signaling has, with regard to bacterial infections, distinct functions in different tissues/organs.…”

“…Deficiency in type I IFN signaling results in an increased bacterial dissemination and is accompanied by diminished production of several pro-inflammatory cytokines, including TNF and IL-6 upon gastric infection using oral gavage (28). Interestingly, type I IFN signaling plays no role in an infection model using food contaminated with L. monocytogenes (30). …”

Neutrophils from Both Susceptible and Resistant Mice Efficiently Kill Opsonized Listeria monocytogenes

“…Hepatic PMN infiltration after foodborne infection is similar in BALB/c and B6 mice. Using the foodborne model of listeriosis in mice, L. monocytogenes colonizes the gut tissue for 24 to 48 h and then spreads systemically to the spleen and liver (2,28). Differences in host susceptibility to infection can readily be observed in the liver, where the number of CFU in susceptible BALB/c mice is significantly greater than in the more resistant B6 mice ( Fig.…”