Conlan J W, North R J
Trudeau Institute, Inc., Saranac Lake, New York 12983.
Infect Immun. 1992 Mar;60(3):951-7. doi: 10.1128/iai.60.3.951-957.1992.
Avirulent mutant strains of Listeria monocytogenes which fail to produce phosphatidylinositol-specific phospholipase C, or which produce reduced amounts of hemolytic listeriolysin O, are incapable of causing progressive infection in normal mice. However, both strains can grow progressively in mice that have been rendered incapable of focusing neutrophils at sites of infection as a result of being treated with monoclonal antibody 5C6, specific for the type 3 complement receptor of myelomonocytic cells. In 5C6-treated mice, phospholipase C-negative and listeriolysin-defective mutant strains of L. monocytogenes, like the wild-type strain, give rise in the liver to large numbers of discrete foci of infected hepatocytes that retain their morphological integrity during the first 24 h, despite their large bacterial burden. In normal mice, in contrast, sites of infection in the liver are indicated by discrete focal accumulations of neutrophils that occupy the space originally occupied by infected hepatocytes. It is apparent that in normal mice neutrophils function to lyse infected hepatocytes and thereby to release L. monocytogenes for ingestion and killing by neutrophils themselves and by macrophages. However, whereas a proportion of wild-type organisms survive this early mechanism of defense to give rise to progressive infection, the phospholipase C-negative organisms are totally eliminated. On the basis of these and other results, it is suggested that virulence factors other than listeriolysin are needed by L. monocytogenes to counteract the early neutrophil-mediated mechanism of defense. Listeriolysin, itself, is an intrinsic virulence factor that allows L. monocytogenes to survive and multiply in a proportion of the fixed phagocytes of the liver (permissive phagocytes) and which enables the organism to go on to infect and replicate in adjacent hepatocytes. It was found that a mutant strain of L. monocytogenes incapable of producing any listeriolysin was incapable of establishing progressive infection, even in 5C6-treated mice.
无法产生磷脂酰肌醇特异性磷脂酶C，或产生溶血李斯特菌溶血素O的量减少的无毒单核细胞增生李斯特菌突变株，无法在正常小鼠中引起进行性感染。然而，这两种菌株都能在因用针对骨髓单核细胞3型补体受体的单克隆抗体5C6治疗而无法在感染部位聚集中性粒细胞的小鼠中进行性生长。在5C6处理的小鼠中，单核细胞增生李斯特菌的磷脂酶C阴性和溶血素缺陷突变株，与野生型菌株一样，在肝脏中产生大量离散的感染肝细胞灶，尽管细菌负荷很大，但在最初24小时内这些病灶仍保持其形态完整性。相比之下，在正常小鼠中，肝脏中的感染部位由占据最初被感染肝细胞占据空间的中性粒细胞离散灶性聚集表示。显然，在正常小鼠中，中性粒细胞的功能是裂解被感染的肝细胞，从而释放单核细胞增生李斯特菌以供中性粒细胞自身和巨噬细胞摄取和杀灭。然而，虽然一部分野生型生物体在这种早期防御机制中存活下来从而引起进行性感染，但磷脂酶C阴性的生物体被完全清除。基于这些和其他结果，有人提出单核细胞增生李斯特菌需要除溶血素之外的毒力因子来对抗早期中性粒细胞介导的防御机制。溶血素本身是一种内在毒力因子，它使单核细胞增生李斯特菌能够在肝脏的一部分固定吞噬细胞（允许性吞噬细胞）中存活和繁殖，并使该生物体能够继续感染相邻肝细胞并在其中复制。研究发现，无法产生任何溶血素的单核细胞增生李斯特菌突变株无法建立进行性感染，即使在5C6处理的小鼠中也是如此。
