Müller A, Hacker J, Brand B C
Institut für Molekulare Infektionsbiologie, Universität Würzburg, Germany.
Infect Immun. 1996 Dec;64(12):4900-6. doi: 10.1128/iai.64.12.4900-4906.1996.
Legionella pneumophila, the causative agent of Legionnaires' disease and Pontiac fever, replicates within and eventually kills human macrophages. In this study, we show that L. pneumophila is cytotoxic to HL-60 cells, a macrophage-like cell line. We demonstrate that cell death mediated by L. pneumophila occurred at least in part through apoptosis, as shown by changes in nuclear morphology, an increase in the proportion of fragmented host cell DNA, and the typical ladder pattern of DNA fragmentation indicative of apoptosis. We further sought to determine whether potential virulence factors like the metalloprotease and the macrophage infectivity potentiator of L. pneumophila are involved in the induction of apoptosis. None of these factors are essential for the induction of apoptosis in HL-60 cells but may be involved in other cytotoxic mechanisms that lead to accidental cell death (necrosis). The ability of L. pneumophila to promote cell death may be important for the initiation of infection, bacterial survival, and escape from the host immune response. Alternatively, the triggering of apoptosis in response to bacterial infection may have evolved as a means of the host immune system to reduce or inhibit bacterial replication.
嗜肺军团菌是军团病和庞蒂亚克热的病原体，可在人类巨噬细胞内复制并最终将其杀死。在本研究中，我们发现嗜肺军团菌对HL - 60细胞（一种巨噬细胞样细胞系）具有细胞毒性。我们证明，嗜肺军团菌介导的细胞死亡至少部分是通过凋亡发生的，这表现为核形态的变化、宿主细胞DNA片段化比例的增加以及指示凋亡的典型DNA片段梯形图谱。我们进一步试图确定嗜肺军团菌的潜在毒力因子如金属蛋白酶和巨噬细胞感染增强因子是否参与凋亡的诱导。这些因子均非HL - 60细胞凋亡诱导所必需，但可能参与导致意外细胞死亡（坏死）的其他细胞毒性机制。嗜肺军团菌促进细胞死亡的能力可能对感染的起始、细菌存活及逃避宿主免疫反应很重要。另外，响应细菌感染而触发的凋亡可能已演变为宿主免疫系统减少或抑制细菌复制的一种方式。
