Uptake and intracellular fate of Francisella tularensis in human macrophages
Uptake and intracellular fate of Francisella tularensis in human macrophages
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DOI：
10.1196/annals.1409.001
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Horwitz, Marcus A.
中科院分区：
文献类型：
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作者：
Clemens, Daniel L.;Horwitz, Marcus A.
土拉热弗朗西丝菌是一种细胞内病原体，在宿主单核吞噬细胞内存活和繁殖。我们已经表明，人类巨噬细胞对细菌的摄取是通过一种新的过程发生的，即“循环吞噬作用”，在这种过程中，细菌被吞噬在一个宽敞的、不对称的伪足环中。而成环吞噬作用对F.在用福尔马林、蛋白酶或热处理土拉菌时，该过程通过用高碘酸盐氧化细菌碳水化合物而被消除，这表明预先形成的表面碳水化合物分子在触发成环吞噬作用中的作用。吸收后，F.土拉热最初存在于细胞外围的一个大空泡中，但这个空泡的大小迅速缩小。新生的F.土拉热菌空泡暂时获得早期内体标记，但随后表现出成熟停滞，表现为仅有限量的溶酶体相关膜糖蛋白（与晚期内体的有限相互作用一致）、与溶酶体不融合和最小酸化。在超微结构研究中，我们观察到F。土拉热菌吞噬体显示一种新的特征，许多吞噬体获得电子致密的纤维状外壳。这种纤维状外套形成水泡和囊泡，随着时间的推移，可以看到被破碎和破坏。随着感染后时间的延长，F.发现土拉热菌游离于巨噬细胞细胞质中，使得在感染后14小时，少于15%的细菌被任何可辨别的吞噬体膜包围。需要进一步的研究，以确定潜在的循环吞噬作用的机制，和成熟的逮捕，纤维状外套的形成，和破坏的吞噬体。
Francisella tularensis is an intracellular pathogen that survives and multiplies within host mononuclear phagocytes. We have shown that uptake of the bacterium by human macrophages occurs by a novel process, "looping phagocytosis," in which the bacterium is engulfed in a spacious, asymmetric, pseudopod loop. Whereas looping phagocytosis is resistant to treatment of the F. tularensis with formalin, proteases, or heat, the process is abolished by oxidation of the bacterial carbohydrates with periodate, suggesting a role for preformed surface carbohydrate molecules in triggering looping phagocytosis. Following uptake, F. tularensis initially resides in a spacious vacuole at the periphery of the cell, but this vacuole rapidly shrinks in size. The nascent F. tularensis vacuole transiently acquires early endosomal markers, but subsequently exhibits an arrested maturation, manifest by only limited amounts of lysosomeassociated membrane glycoproteins (consistent with limited interaction with late endosomes), nonfusion with lysosomes, and minimal acidification. In ultrastructural studies, we have observed that the F. tularensis phagosome displays a novel feature in that many of the phagosomes acquire an electron dense fibrillar coat. This fibrillar coat forms blebs and vesicles, and with time, is seen to be fragmented and disrupted. With increasing time after infection, increasing numbers of the F. tularensis are found free in the macrophage cytoplasm, such that by 14 h after infection, less than 15% of the bacteria are surrounded by any discernible phagosomal membrane. Further research is needed to determine the mechanisms underlying looping phagocytosis, and the maturational arrest, fibrillar coat formation, and disruption of the phagosome.