Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 200, Issue 9, Pages 1135-1143Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20041408
Keywords
trypomastigote; invasion; intracellular; fusion; lysosome
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Funding
- NIAID NIH HHS [R37 AI034867, R01 AI034867, AI34867] Funding Source: Medline
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Trypomastigotes, the highly motile infective forms of Trypanosouta cruzi, are capable of infecting several cell types. Invasion occurs either by direct recruitment and fusion of lysosomes at the plasma membrane, or through invagination of the plasma membrane followed by intracellular fusion with lysosomes. The lysosome-like parasitophorous vacuole is subsequently disrupted, releasing the parasites for replication in the cytosol. The role of this early residence within lysosomes in the intracellular cycle of T. cruzi has remained unclear. For several other cytosolic pathogens, survival inside host cells depends on an early escape from phagosomes before lysosomal fusion. Here, we show that when lysosome-mediated T. cruzi invasion is blocked through phosophoinositide 3-kinase inhibition, a significant fraction of the internalized parasites are not subsequently retained inside host cells for a productive infection. A direct correlation was observed between the lysosomal fusion rates after invasion and the intracellular retention of trypomastigotes. Thus, formation of a parasitophorous vacuole with lysosomal properties is essential for preventing these highly motile parasites from exiting host cells and for allowing completion of the intracellular life cycle.
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