Hall B F, Furtado G C, Joiner K A
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510-8056.
J Immunol. 1991 Dec 15;147(12):4313-21.
Trypanosoma cruzi, an obligate intracellular protozoan parasite, exhibits developmental regulation of virulence. Although both noninfective epimastigote and infective trypomastigote stages of T. cruzi enter phagocytic cells via the formation of a parasitophorous vacuole (PV), only the latter developmental stages survive ingestion and perpetuate the infection. To determine whether the membrane composition of PV surrounding these different stages might contribute to differences in the outcome of infection, we identified selected membrane constituents by immunofluorescence and intracellular radioiodination, and studied their incorporation into PV. Complement receptors (CR3) are incorporated preferentially into the PV membrane surrounding serum-opsonized epimastigotes but not culture-derived metacyclic trypomastigotes. FcR are not preferentially incorporated into PV membranes unless epimastigotes or culture-derived metacyclic trypomastigotes are opsonized with anti-T. cruzi antibody. PV surrounding either parasite stage contain beta 1 integrins and lysosomal membrane glycoproteins (lgp). These results indicate that the plasma membrane glycoproteins incorporated into the surrounding PV membrane differ depending upon the stage of parasite being internalized, and that these differences reflect, at least in part, selective ligation of cell surface receptors mediating uptake. Furthermore, they imply that although virulent trypomastigote stages may avoid host cell uptake by conventional phagocytic receptors, i.e., CR3 or FcR, they do not escape fusion with an lgp-containing vacuole where they could still be exposed to lysosomal antimicrobial mechanisms.
克氏锥虫是一种专性细胞内原生动物寄生虫,具有毒力的发育调控。尽管克氏锥虫的非感染性前鞭毛体阶段和感染性锥鞭毛体阶段都通过形成寄生泡(PV)进入吞噬细胞,但只有后者的发育阶段能在被吞噬后存活并使感染持续。为了确定围绕这些不同阶段的PV膜组成是否可能导致感染结果的差异,我们通过免疫荧光和细胞内放射性碘化鉴定了选定的膜成分,并研究了它们掺入PV的情况。补体受体(CR3)优先掺入围绕血清调理的前鞭毛体的PV膜中,但不掺入培养来源的循环后期锥鞭毛体的PV膜中。除非前鞭毛体或培养来源的循环后期锥鞭毛体用抗克氏锥虫抗体进行调理,否则FcR不会优先掺入PV膜中。围绕任一寄生虫阶段的PV都含有β1整合素和溶酶体膜糖蛋白(lgp)。这些结果表明,掺入周围PV膜的质膜糖蛋白因被内化的寄生虫阶段而异,并且这些差异至少部分反映了介导摄取的细胞表面受体的选择性连接。此外,这意味着尽管有致病性的锥鞭毛体阶段可能通过传统的吞噬受体(即CR3或FcR)避免被宿主细胞摄取,但它们无法逃脱与含有lgp的液泡融合,在那里它们仍可能暴露于溶酶体抗菌机制。