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Title: Extracellular amastigotes of Trypanosoma cruzi are potent inducers of phagocytosis in mammalian cells
Authors: Fernandes, Maria Cecilia
Flannery, Andrew R.
Andrews, Norma
Mortara, Renato Arruda [UNIFESP]
Univ Maryland
Universidade Federal de São Paulo (UNIFESP)
Issue Date: 1-Jun-2013
Publisher: Wiley-Blackwell
Citation: Cellular Microbiology. Hoboken: Wiley-Blackwell, v. 15, n. 6, p. 977-991, 2013.
Abstract: The protozoan parasite Trypanosoma cruzi, the aetiological agent of Chagas' disease, has two infective life cycle stages, trypomastigotes and amastigotes. While trypomastigotes actively enter mammalian cells, highly infective extracellular amastigotes (type IT.cruzi) rely on actin-mediated uptake, which is generally inefficient in non-professional phagocytes. We found that extracellular amastigotes (EAs) of T.cruziG strain (type I), but not Y strain (type II), were taken up 100-fold more efficiently than inert particles. Mammalian cell lines showed levels of parasite uptake comparable to macrophages, and extensive actin recruitment and polymerization was observed at the site of entry. EA uptake was not dependent on parasite-secreted molecules and required the same molecular machinery utilized by professional phagocytes during large particle phagocytosis. Transcriptional silencing of synaptotagmin VII and CD63 significantly inhibited EA internalization, demonstrating that delivery of supplemental lysosomal membrane to form the phagosome is involved in parasite uptake. Importantly, time-lapse live imaging using fluorescent reporters revealed phagosome-associated modulation of phosphoinositide metabolism during EA uptake that closely resembles what occurs during phagocytosis by macrophages. Collectively, our results demonstrate that T.cruziEAs are potent inducers of phagocytosis in non-professional phagocytes, a process that may facilitate parasite persistence in infected hosts.
ISSN: 1462-5814
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