Novel strategy in Trypanosoma cruzi cell invasion: Implication of cholesterol and host cell microdomains

Novel strategy in Trypanosoma cruzi cell invasion: Implication of cholesterol and host cell microdomains

Author Fernandes, Maria Cecilia Google Scholar
Cortez, Mauro Google Scholar
Geraldo Yoneyama, Kelly Aparecida Google Scholar
Straus, Anita Hilda Google Scholar
Yoshida, Nobuko Google Scholar
Mortara, Renato Arruda Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Trypanosoma cruzi, the etiological agent of Chagas' disease, is an obligatory intracellular parasite in the mammalian host. in order to invade a wide variety of mammalian cells, T cruzi engages parasite components that are differentially expressed among strains and infective forms. Because the identification of putative protein receptors has been particularly challenging, we investigated whether cholesterol and membrane rafts, sterol- and sphingolipid-enriched membrane domains, could be general host surface components involved in invasion of metacyclic trypomastigotes and extracellular amastigotes of two parasite strains with distinct infectivities. HeLa or Vero cells treated with methyl-beta-cyclodextrin (M beta CD) are less susceptible to invasion by both infective forms, and the effect was dose-dependent for trypomastigote but not amastigote invasion. Moreover, treatment of parasites with MPCD only inhibited trypomastigote invasion. Filipin labeling confirmed that host cell cholesterol concentrated at the invasion sites. Binding of a cholera toxin B subunit (CTX-B) to ganglioside GM1, a marker of membrane rafts, inhibited parasite infection. Cell labeling with CTX-B conjugated to fluorescein isothiocyanate revealed that not only cholesterol but also GM1 is implicated in parasite entry. These findings thus indicate that microdomains present in mammalian cell membranes, that are enriched in cholesterol and GM1, are involved in invasion by T cruzi infective forms. (c) 2007 Australian Society for Parasitology Inc. Published by Elsevier B.V. All rights reserved.
Keywords Trypanosoma cruzi
trypomastigote
amastigote
membrane rafts
cholesterol
cell invasion
Language English
Date 2007-11-01
Published in International Journal for Parasitology. Oxford: Pergamon-Elsevier B.V., v. 37, n. 13, p. 1431-1441, 2007.
ISSN 0020-7519 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1431-1441
Origin http://dx.doi.org/10.1016/j.ijpara.2007.04.025
Access rights Closed access
Type Article
Web of Science ID WOS:000250182800002
URI http://repositorio.unifesp.br/handle/11600/30126

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