Lerm M, Holm A, Seiron A, Särndahl E, Magnusson K-E, Rasmusson B
Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
Infect Immun. 2006 May;74(5):2613-8. doi: 10.1128/IAI.74.5.2613-2618.2006.
Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase C alpha. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation.
杜氏利什曼原虫前鞭毛体通过抑制吞噬体成熟在巨噬细胞吞噬体内存活。前鞭毛体上的主要表面糖缀合物脂磷壁酸(LPG)对其存活至关重要,并介导在吞噬体周围形成F-肌动蛋白的保护壳。先前的研究表明,这种作用涉及对蛋白激酶Cα的抑制。本研究表明,功能性Cdc42和Rac1是杜氏利什曼原虫吞噬体周围F-肌动蛋白形成所必需的。此外,我们提供的数据表明,含有LPG缺陷型杜氏利什曼原虫的吞噬体无法诱导F-肌动蛋白积累,在具有永久活性形式的Cdc42和Rac1的巨噬细胞中,其吞噬体周围F-肌动蛋白水平升高且吞噬体成熟受损。我们得出结论,杜氏利什曼原虫利用Cdc42和Rac1在其吞噬体周围构建一层F-肌动蛋白保护壳,以防止吞噬体成熟。