Fischer Silke F, Vier Juliane, Müller-Thomas Catharina, Häcker Georg
Institute for Medical Microbiology, Technische Universität München, D-81675 Munich, Germany.
Microbes Infect. 2006 Mar;8(3):662-9. doi: 10.1016/j.micinf.2005.08.016. Epub 2006 Jan 13.
Legionella pneumophila, the agent of human Legionnaire's disease is a Gram-negative, rod-shaped bacterium. During infection, the bacteria invade human cells and replicate intracellularly. L. pneumophila can induce apoptosis in human myeloid and epitheloid cells and this may contribute to the development of pathology and disease. However, the molecular mechanism of apoptosis induction is still uncertain. Here we investigate this process. Legionella efficiently induced apoptosis in myeloid cells, T cells and fibroblasts. Induction of apoptosis involved activation of the initiator caspase-9 and effector caspases. Caspase activity was required for cell death. Analysis of mutant cells showed that the death receptor pathway was not involved in Legionella-induced apoptosis. Surprisingly, caspase activity was found almost exclusively in cells that did not harbor bacteria. Infection with Legionella caused the activation of the pro-apoptotic protein Bax and the release of cytochrome c. Mouse embryonic fibroblasts deficient for Bax and/or Bak were protected from Legionella-induced caspase activation. These results show a clear contribution of the mitochondrial pathway to Legionella-induced apoptosis.
嗜肺军团菌是人类军团病的病原体，是一种革兰氏阴性、杆状细菌。在感染过程中，该细菌侵入人体细胞并在细胞内复制。嗜肺军团菌可诱导人类髓样细胞和上皮样细胞凋亡，这可能有助于病理和疾病的发展。然而，诱导凋亡的分子机制仍不确定。在此我们研究这一过程。军团菌能有效诱导髓样细胞、T细胞和成纤维细胞凋亡。凋亡的诱导涉及起始半胱天冬酶-9和效应半胱天冬酶的激活。细胞死亡需要半胱天冬酶活性。对突变细胞的分析表明，死亡受体途径不参与军团菌诱导的凋亡。令人惊讶的是，半胱天冬酶活性几乎只在未携带细菌的细胞中发现。感染军团菌会导致促凋亡蛋白Bax的激活和细胞色素c的释放。缺乏Bax和/或Bak的小鼠胚胎成纤维细胞可免受军团菌诱导的半胱天冬酶激活。这些结果表明线粒体途径对军团菌诱导的凋亡有明显作用。
