The autophagic pathway is a key component in the lysosomal dependent entry of Trypanosoma cruzi into the host cell.
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.
Romano
Patricia S
PS
Laboratorio de Biología Celular y Molecular-Instituto de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo-CONICET, Mendoza, Argentina.
Arboit
María A
MA
Vázquez
Cristina L
CL
Colombo
María I
MI
D000818:Animals; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D016466:CHO Cells; D002454:Cell Differentiation; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000166:cytology / Q000469:parasitology; D006790:Host-Parasite Interactions; D008247:Lysosomes / Q000469:parasitology*; D051379:Mice; D010588:Phagosomes / Q000378:metabolism / Q000469:parasitology; D022161:Transport Vesicles / Q000378:metabolism / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000166:cytology* / Q000502:physiology*; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology
D015415:Biomarkers