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

单核细胞增生李斯特菌是一种兼性胞内细菌，在巨噬细胞内增殖，并诱导宿主产生强烈的细胞免疫。目前还不清楚是什么样的毒力因子导致细胞内寄生。另一个问题是为什么诱导细胞介导的免疫只能通过用活菌免疫而不是用灭活的bacteries.In本研究中，我们比较了各种菌株的单核细胞增生李斯特菌的致死率或在小鼠中的生长和在巨噬细胞中繁殖的能力。结果发现，这些参数存在显着的株间差异。在几个候选的毒力因子，溶血素的产生能力是高度相关的，不仅致病性，而且诱导细胞介导的免疫能力。但溶血素阳性和阴性菌株诱导免疫T细胞的抗原性无明显差异。在用活的 ...更多信息 结果表明，在溶血素阴性菌株的细胞或用灭活细菌免疫的那些细胞中，抗原特异性T细胞的成熟在免疫诱导的初始阶段被阻滞。杀死的细菌或活的hly阴性菌株不能诱导活性细胞介导的免疫，这归因于对巨噬细胞IL-1产生的无效诱导，因为只有hly阳性菌株的活细胞才能在培养的巨噬细胞中诱导可溶性和膜相关形式的IL-1以及IL-1 mRNA。纯化的李斯特菌溶血素能够在体外诱导巨噬细胞IL- 1，这一事实进一步支持了这一想法。用本身不能诱导T细胞成熟的灭活细菌疫苗免疫小鼠后，将重组IL-1（rIL-1）给予小鼠，可以实现抗原特异性T细胞的功能性成熟。溶血素是单核细胞增生李斯特菌主要毒力因子，通过其在体内免疫应答的初始阶段诱导大量IL-1的能力介导免疫。少

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