Sibley L D, Weidner E, Krahenbuhl J L
Nature. 1985;315(6018):416-9. doi: 10.1038/315416a0.
Toxoplasma gondii belongs to a group of highly virulent intracellular parasites that reside in host cell vacuoles which resist typical phagosome-lysosome fusion. Live Toxoplasma replicate prodigiously within modified phagocytic vacuoles formed during invagination of the host plasma membrane. In contrast, heat-killed Toxoplasma or specific antibody (heat-inactivated)-coated live Toxoplasma-containing vacuoles readily undergo lysosome fusion and digestion in normal macrophages. Of newly recognized significance to Toxoplasma survival is the microbicidal effect of phagosome acidification, which reportedly can occur independently of fusion with other acidic vesicles. We report here that modified live Toxoplasma-containing vacuoles fail to acidify in normal macrophages, as indicated by the sensitive pH probe fluorescein. In contrast, when live Toxoplasma are coated with specific antibody (heat-inactivated), they trigger phagosome acidification when entering normal macrophages. A similar acidification is observed when normal phagocytes ingest dead Toxoplasma. Extracellular Toxoplasma are highly susceptible to acidic pH conditions, indicating that the acidification block in the modified vacuoles may be important for intracellular survival.
弓形虫属于一类高毒力的细胞内寄生虫，它们寄生于宿主细胞液泡中，这些液泡可抵抗典型的吞噬体-溶酶体融合。活的弓形虫在宿主质膜内陷过程中形成的修饰吞噬泡内大量繁殖。相比之下，热灭活的弓形虫或包被有特异性抗体（热灭活）的含活弓形虫的液泡在正常巨噬细胞中很容易发生溶酶体融合和消化。对弓形虫生存具有新认识意义的是吞噬体酸化的杀菌作用，据报道这种作用可独立于与其他酸性囊泡的融合而发生。我们在此报告，用灵敏的pH探针荧光素检测表明，正常巨噬细胞中含修饰活弓形虫的液泡未能酸化。相反，当活弓形虫包被有特异性抗体（热灭活）时，它们进入正常巨噬细胞时会引发吞噬体酸化。当正常吞噬细胞摄取死的弓形虫时也观察到类似的酸化现象。细胞外的弓形虫对酸性pH条件高度敏感，这表明修饰液泡中的酸化阻断可能对细胞内存活很重要。
