Differences in Gamma Interferon Production Induced by Listeriolysin O and Ivanolysin O Result in Different Levels of Protective Immunity in Mice Infected with Listeria monocytogenes and Listeria ivanovii

Abstract

ABSTRACT Two pathogenic species in the genus Listeria, Listeria monocytogenes and Listeria ivanovii , are characterized by the production of hemolysins belonging to cholesterol-dependent cytolysins, listeriolysin O (LLO) and ivanolysin O (ILO), respectively. LLO, produced by L. monocytogenes , is able to induce gamma interferon (IFN-γ) production and contributes to the generation of Th1-dependent protective immunity. On the other hand, nothing is known about the role of ILO, produced by L. ivanovii , in this regard. In this study, we immunized mice with 0.1 50% lethal dose (LD 50 ) of L. monocytogenes and L. ivanovii. Protective immunity against a challenge with 10 LD 50 was generated in mice infected with L. monocytogenes , whereas L. ivanovii infection did not induce protection. After immunization, the level of IFN-γ in serum samples was increased in mice given L. monocytogenes but not in those given L. ivanovii. To determine the IFN-γ-inducing activity of cytolysins, recombinant protein was constructed. Recombinant ILO exhibited significantly lower IFN-γ-inducing activity than LLO. By comparing the IFN-γ-inducing activity of a chimera incorporating LLO and ILO, it was found that domains 1 to 3 of LLO were critical for IFN-γ-inducing activity while the counterpart in ILO was unable to induce cytokine production. These results suggested that the weak ability of ILO to induce IFN-γ production is responsible for the failure of L. ivanovii to generate effective protective immunity.