Inhibition of phagolysosomal biogenesis by the Leishmania lipophosphoglycan.
Inhibition of phagolysosomal biogenesis by the Leishmania lipophosphoglycan.
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DOI：
10.1084/jem.185.12.2061
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发表时间：
1997-06-16
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尽管原生动物寄生虫利什曼原虫的无鞭毛体在巨噬细胞的酸性吞噬溶酶体液泡内增殖，但在感染起始期间杜氏利什曼原虫前鞭毛体诱导的液泡的特征却很少。在此，证据表明这些寄生液泡与内吞细胞器的相互作用非常有限。相反，缺乏细胞表面脂磷酸聚糖（LPG）的杜氏乳杆菌突变体周围形成的液泡与内体和溶酶体广泛融合。使用两种不同的方法证明了 LPG 重复单元在抑制吞噬体-内体融合中的作用。首先，LPG缺陷型C3PO突变体的基因互补恢复了其抑制吞噬体-内体融合的能力，达到与野生型前鞭毛体相似的程度。其次，用纯化的杜氏乳杆菌 LPG 调理 C3PO 突变细胞也赋予该突变体抑制吞噬体-内体融合的能力。由于 LPG 对于感染巨噬细胞至关重要，因此这些结果表明，LPG 重复单元对吞噬溶酶体生物发生的抑制代表了前鞭毛体用于建立感染的巨噬细胞内生存策略。
Whereas amastigotes of the protozoan parasite Leishmania proliferate inside acidic phagolysosomal vacuoles of the macrophage, vacuoles induced by Leishmania donovani promastigotes during initiation of infection are poorly characterized. Here, evidence is presented that interaction of these parasitophorous vacuoles with endocytic organelles is very limited. In contrast, vacuoles formed around L. donovani mutants lacking the cell surface lipophosphoglycan (LPG) fuse extensively with endosomes and lysosomes. The role of LPG repeating units in the inhibition of phagosome–endosome fusion was demonstrated using two different approaches. First, genetic complementation of the LPG-defective C3PO mutant restored its ability to inhibit phagosome–endosome fusion to a degree similar to that of wild-type promastigotes. Second, opsonization of C3PO mutant cells with purified L. donovani LPG also conferred to this mutant the ability to inhibit phagosome–endosome fusion. Inasmuch as LPG is essential for infecting macrophages, these results suggest that inhibition of phagolysosomal biogenesis by LPG repeating units represents an intramacrophage survival strategy used by promastigotes to establish infection.