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

胞内细菌单核细胞增生李斯特菌的毒力因子和诱导细胞介导免疫的机制分析。

基本信息

批准号：
63480152
负责人：
MITSUYAMA Masao
金额：
$ 4.22万
依托单位：
Niigata University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

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

单核细胞增多性李斯特菌是一种兼性细胞内细菌，它在巨噬细胞内繁殖，并在受感染的宿主中诱导强烈的细胞介导的免疫。目前尚不清楚哪种毒力因子有助于细胞内寄生。另一个问题是为什么会诱导细胞内寄生。 -介导的免疫只能通过用活细菌免疫来实现，而不是用灭活细菌来实现。在本研究中，我们比较了单核细胞增生利斯特氏菌的各种菌株对小鼠的致死率或生长情况以及发现在这些参数中存在显着的毒力因子的菌株间差异，产生溶血素的能力不仅与致病性而且与诱导细胞增殖的能力高度相关。然而，在用溶血素阴性菌株的活细胞免疫的小鼠中，溶血素阳性菌株和阴性菌株之间诱导免疫 T 细胞的抗原性没有显着差异。用灭活的细菌进行免疫，结果表明，抗原特异性 T 细胞的成熟在免疫诱导的初始阶段被抑制。灭活的细菌或活的 hly 阴性菌株无法诱导活性细胞介导的免疫，这是由于免疫诱导的无效。巨噬细胞 IL-1 的产生，因为 hly 阳性菌株的所有活细胞都可以在培养的巨噬细胞和 IL-1 mRNA 中诱导可溶性和膜相关形式的 IL-1，纯化的李斯特菌这一事实进一步支持了这一观点。溶血素能够在体外诱导巨噬细胞IL-1，当给用灭活细菌疫苗免疫后的小鼠施用重组IL-1（rIL-1）时，溶血素本身不能有效诱导T细胞成熟，从而导致抗原功能成熟。 -可以实现特异性T细胞。从本研究中获得的这些结果可以清楚地看出，溶血素是单核细胞增生李斯特氏菌的主要毒力因子，也是单核细胞增生李斯特氏菌不可缺少的毒力因子。其在体内免疫反应的初始阶段诱导大量IL-1的能力较少，从而产生特异性细胞介导的免疫。