Analysis of virulence factor and the mechanisms for induction of cell-mediated immunity by intracellular bacterium, Listeria monocytogenes.

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Listeria monocytogenes is one of facultative intracellular bacteria, which multiply inside macrophages and induce a strong cell-mediated immunity in the infected host. It is not still clear what sort of virulence factor is contributing to intracellular parasitism. Another question is why the induction of cell-mediated immunity is achieved only by immunization with viable bacteria but not with killed bacteria.In the present study, we compared various strains of L.monocytogenes with respect to lethality to or growth in mice and the ability to multiply in macropahges. It was found that there was a marked inter-strain difference in these parameters. Among several candidates for virulence factor, the ability to produce hemolysin was highly related not only to pathogenicity but also to the ability to induce cell-mediated immunity. However, there was no significant difference in antigenicity to elicit immune T cells between hemolysin positive and negative strains. In mice immunized with viabl … More e cells of hemolysin-negative strain or in those immunized with killed bacteria, it was shown that maturation of antigen specific T cells were arrested at the initial stage of immune induction. The inability of killed bacteria or viable hly-negative strain to induce active cell-mediated immunity was attributable to an ineffective induction of macrophage IL-1 production, since all only viable cells of hly-positive strains could induce soluble and membrane-associated forms of IL-1 in cultured macrophages and IL-1 mRNA as well. This idea was further supported by the fact that purified Listeria hemolysin is capable of inducing macrophage IL- 1 in vitro. When recombinant IL-1 (rIL-1) was administered to mice after immunization with killed bacterial vaccine, which is ineffective in the induction of T cell maturation by itself, functional maturation of antigen-specific T cells could be achieved.From these results obtained in this study, it became clear that hemolysin is a major virulence factor for L.monocytogenes and also is indispensable for generation of specific cell-mediated immunity by its ability to induce a large amount of IL-1 in the initial phase of immune response in vivo. Less