Salassa Betiana Nebaí, Cueto Juan Agustín, Gambarte Tudela Julián, Romano Patricia Silvia
Laboratorio de Biología de Trypanosoma cruzi la célula hospedadora, Instituto de Histología y Embriologìa, Consejo Nacional de Investigaciones Científicas y Técnicas (IHEM-CONICET), Universidad Nacional de Cuyo, Mendoza, Argentina.
Facultad de Odontología, Universidad Nacional de Cuyo, Mendoza, Argentina.
Front Cell Infect Microbiol. 2020 Oct 29;10:536985. doi: 10.3389/fcimb.2020.536985. eCollection 2020.
is the parasite causative of Chagas disease, a highly disseminated illness endemic in Latin-American countries. has a complex life cycle that involves mammalian hosts and insect vectors both of which exhibits different parasitic forms. Trypomastigotes are the infective forms capable to invade several types of host cells from mammals. infection process comprises two sequential steps, the formation and the maturation of the parasitophorous vacuole. Host Rab GTPases are proteins that control the intracellular vesicular traffic by regulating budding, transport, docking, and tethering of vesicles. From over 70 Rab GTPases identified in mammalian cells only two, Rab5 and Rab7 have been found in the vacuole to date. In this work, we have characterized the role of the endocytic, recycling, and secretory routes in the infection process in CHO cells, by studying the most representative Rabs of these pathways. We found that endocytic Rabs are selectively recruited to the vacuole of , among them Rab22a, Rab5, and Rab21 right away after the infection followed by Rab7 and Rab39a at later times. However, neither recycling nor secretory Rabs were present in the vacuole membrane at the times studied. Interestingly loss of function of endocytic Rabs by the use of their dominant-negative mutant forms significantly decreases infection. These data highlight the contribution of these proteins and the endosomal route in the process of infection.
是恰加斯病的致病寄生虫,恰加斯病是一种在拉丁美洲国家广泛传播的地方性疾病。它具有复杂的生命周期,涉及哺乳动物宿主和昆虫媒介,两者都呈现出不同的寄生形式。锥鞭毛体是能够侵入哺乳动物多种类型宿主细胞的感染形式。感染过程包括两个连续步骤,即吞噬泡的形成和成熟。宿主Rab GTP酶是通过调节囊泡的出芽、运输、对接和拴系来控制细胞内囊泡运输的蛋白质。在哺乳动物细胞中鉴定出的70多种Rab GTP酶中,迄今为止仅在吞噬泡中发现了两种,即Rab5和Rab7。在这项工作中,我们通过研究这些途径中最具代表性的Rab,表征了内吞、再循环和分泌途径在锥虫感染CHO细胞过程中的作用。我们发现,内吞Rab在感染后立即被选择性地募集到锥虫的吞噬泡中,其中包括Rab22a、Rab5和Rab21,随后在较晚时间募集到Rab7和Rab39a。然而,在所研究的时间内,再循环Rab和分泌Rab均未出现在吞噬泡膜中。有趣的是,通过使用其显性负突变形式使内吞Rab功能丧失会显著降低锥虫感染。这些数据突出了这些蛋白质和内体途径在锥虫感染过程中的作用。