title: Actin cytoskeleton-dependent and -independent host cell invasion by Trypanosoma cruzi is mediated by distinct parasite surface molecules.
abstract: The disassembly of host cell actin cytoskeleton as a facilitator of Trypanosoma cruzi invasion has been reported by some authors, while other workers claim that it instead inhibits internalization of the parasite. In this study we aimed at elucidating the basis of this discrepancy. We performed experiments with metacyclic trypomastigotes of T. cruzi strains G and CL, which differ markedly in infectivity and enter target cells by engaging the surface molecules gp35/50 and gp82, respectively, which have signaling activity. Treatment of HeLa cells with the F-actin-disrupting drug cytochalasin D or latrunculin B inhibited the invasion by strain G but not the invasion by strain CL. In contrast to cells penetrated by strain CL, which were previously shown to have a disrupted actin cytoskeleton architecture, no such alteration was observed in HeLa cells invaded by strain G, and parasites were found to be closely associated with target cell actin. Coinfection with enteroinvasive Escherichia coli (EIEC), which recruits host cell actin for internalization, drastically reduced entry of strain CL into HeLa cells but not entry of strain G. In contrast to gp82 in its recombinant form, which induces disruption of F-actin and inhibits EIEC invasion, purified mucin-like gp35/50 molecules promoted an increase in EIEC uptake by HeLa cells. These data, plus the finding that drugs that interfere with mammalian cell signaling differentially affect the internalization of metacyclic forms of strains G and CL, indicate that the host cell invasion mediated by gp35/50 is associated with signaling events that favor actin recruitment, in contrast to gp82-dependent invasion, which triggers the signaling pathways leading to disassembly of F-actin.
authors.affiliation: Escola Paulista de Medicina, Universidade Federal de São Paulo, R. Botucatu, 862, 6 andar, 04023-062, São Paulo, S.P. Brasil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Ferreira
authors.forename: Mauro
authors.initials: M
authors.lastname: Cortez
authors.forename: Vanessa D
authors.initials: VD
authors.lastname: Atayde
authors.forename: Nobuko
authors.initials: N
authors.lastname: Yoshida
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D009077:Mucins / Q000276:immunology / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D053778:Thiazolidines / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D009077:Mucins; D011994:Recombinant Proteins; D053778:Thiazolidines; D015638:Cytochalasin D; C037068:latrunculin B