Romano Patricia S, Arboit María A, Vázquez Cristina L, Colombo María I
Laboratorio de Biología Celular y Molecular-Instituto de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo-CONICET, Mendoza, Argentina.
Autophagy. 2009 Jan;5(1):6-18. doi: 10.4161/auto.5.1.7160.
The etiologic agent of Chagas disease, Trypanosoma cruzi, infects mammalian cells activating a signal transduction cascade that leads to the formation of its parasitophorous vacuole. Previous works have demonstrated the crucial role of lysosomes in the establishment of T. cruzi infection. In this work we have studied the possible relationship between this parasite and the host cell autophagy. We show, for the first time, that the vacuole containing T. cruzi (TcPV) is decorated by the host cell autophagic protein LC3. Furthermore, live cell imaging experiments indicate that autolysosomes are recruited to parasite entry sites. Interestingly, starvation or pharmacological induction of autophagy before infection significantly increased the number of infected cells whereas inhibitors of this pathway reduced the invasion. In addition, the absence of Atg5 or the reduced expression of Beclin 1 -- two proteins required at the initial steps of autophagosome formation -- limited parasite entry and reduced the association between TcPV and the classical lysosomal marker Lamp-1. These results indicate that mammalian autophagy is a key process that favors the colonization of T. cruzi in the host cell.
恰加斯病的病原体克氏锥虫感染哺乳动物细胞，激活信号转导级联反应，导致其寄生泡的形成。先前的研究表明溶酶体在克氏锥虫感染的建立过程中起着关键作用。在这项工作中，我们研究了这种寄生虫与宿主细胞自噬之间可能存在的关系。我们首次表明，含有克氏锥虫的液泡（TcPV）被宿主细胞自噬蛋白LC3修饰。此外，活细胞成像实验表明自噬溶酶体被招募到寄生虫进入位点。有趣的是，感染前饥饿或自噬的药理学诱导显著增加了感染细胞的数量，而该途径的抑制剂则减少了入侵。此外，Atg5的缺失或Beclin 1表达的降低——自噬体形成初始步骤所需的两种蛋白质——限制了寄生虫的进入，并减少了TcPV与经典溶酶体标志物Lamp-1之间的关联。这些结果表明，哺乳动物自噬是一个有利于克氏锥虫在宿主细胞中定殖的关键过程。
