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Apoptosis in Macrophages and Alveolar Epithelial Cells during Early Stages of Infection by Legionella pneumophila and Its Role in Cytopathogenicity

机译:嗜肺军团菌感染早期巨噬细胞和肺泡上皮细胞的凋亡及其在细胞致病性中的作用

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The hallmark of Legionnaires’ disease is intracellular replication of Legionella pneumophila within cells in the alveolar spaces. Cytopathogenicity of this bacterium to the host cell has been well demonstrated, but the mechanisms of host cell death due to infection by L. pneumophila are not well understood. In this study, induction of apoptosis in macrophages and alveolar epithelial cells by L. pneumophila during early stages of infection was confirmed by using multiple criteria, including DNA fragmentation by agarose gel electrophoresis, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, surface exposure of phosphatidylserine, and cellular morphology by transmission electron microscopy. Induction of nuclear apoptosis in L. pneumophila-infected macrophages is mediated by activation of the caspase cascade death machinery. We provide genetic and biochemical evidence thatL. pneumophila-induced apoptosis in macrophages and alveolar epithelial cells does not require intracellular bacterial replication or new protein synthesis. In addition, extracellularL. pneumophila is capable of inducing apoptosis. Furthermore, induction of apoptosis by L. pneumophilacorrelates with cytopathogenicity. We conclude that L. pneumophila-induced apoptosis in macrophages and alveolar epithelial cells plays an important role in cytopathogenicity to the host cell during early stages of infection.
机译:退伍军人症的标志是肺泡军团菌在肺泡腔内的细胞内复制。该细菌对宿主细胞的细胞致病性已得到充分证明,但宿主细胞因 L感染而死亡的机制。肺炎不是很清楚。在这项研究中, L诱导巨噬细胞和肺泡上皮细胞凋亡。通过多种标准证实了感染早期的嗜肺性肺炎,包括琼脂糖凝胶电泳的DNA片段化,末端脱氧核苷酸转移酶介导的dUTP缺口末端标记,磷脂酰丝氨酸的表面暴露以及透射电子显微镜观察的细胞形态。诱导 L细胞核凋亡。肺炎支原体感染的巨噬细胞是由半胱天冬酶级联死亡机制的激活介导的。我们提供 L的遗传和生化证据。肺炎支原体诱导的巨噬细胞和肺泡上皮细胞凋亡不需要细胞内细菌复制或新的蛋白质合成。另外,细胞外L。肺炎能够诱导细胞凋亡。此外,通过 L诱导细胞凋亡。肺炎与细胞致病性相关。我们得出结论, L。肺炎巨噬细胞诱导的巨噬细胞和肺泡上皮细胞凋亡在感染初期对宿主细胞的致病性中起重要作用。

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