Roles of caspase-1 in Listeria infection in mice

Abstract

Caspase-1 [IL-1β-converting enzyme (ICE)] processes substrate precursor molecules to yield the biologically active form of IL-1β and IL-18, both of which are considered to play important roles in the host defense by activation of both innate and adaptive immunity. We evaluated the immune response of caspase-1-/- mice to Listeria monocytogenes (LM) infection. LM eradication in the early phase of infection was impaired in the mutant mice with a prominent decrease in IL-18 and IFN-γ production, but not in IL-12. Caspase-1-/- spleen cells including dendritic cells and NK cells produced less IFN-γ in response to heat-killed LM than wild-type cells in vitro. IFN-γ production and bactericidal activity in LM-infected caspase-1-/- mice was reconstituted to normal levels by adding back IL-18 at the initial phase of infection, suggesting that the lack of this cytokine is primarily responsible for the susceptibility of caspase-1-/- mice against LM infection. Moreover, IFN-γ injection of caspase-1-/- mice corrected the deficiency in pathogen clearance. In contrast, LM-specific acquired immunity in caspase-1-/- mice was normal and they successfully cleared the pathogen following secondary infection, in spite of a moderate skewing of cytokine profile to Th2 when compared to wild-type mice. These data shed light on the importance of caspase-1-mediated IL-18 processing in innate immunity against facultative intracellular pathogens.