title: Trypanosoma cruzi immune evasion mediated by host cell-derived microvesicles.
abstract: The innate immune system is the first mechanism of vertebrate defense against pathogen infection. In this study, we present evidence for a novel immune evasion mechanism of Trypanosoma cruzi, mediated by host cell plasma membrane-derived vesicles. We found that T. cruzi metacyclic trypomastigotes induced microvesicle release from blood cells early in infection. Upon their release, microvesicles formed a complex on the T. cruzi surface with the complement C3 convertase, leading to its stabilization and inhibition, and ultimately resulting in increased parasite survival. Furthermore, we found that TGF-β-bearing microvesicles released from monocytes and lymphocytes promoted rapid cell invasion by T. cruzi, which also contributed to parasites escaping the complement attack. In addition, in vivo infection with T. cruzi showed a rapid increase of microvesicle levels in mouse plasma, and infection with exogenous microvesicles resulted in increased T. cruzi parasitemia. Altogether, these data support a role for microvesicles contributing to T. cruzi evasion of innate immunity.
authors.affiliation: Laboratório de Biologia Molecular de Parasitas e Vetores, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil.
authors.forename: Igor
authors.initials: I
authors.lastname: Cestari
authors.forename: Ephraim
authors.initials: E
authors.lastname: Ansa-Addo
authors.forename: Poliana
authors.initials: P
authors.lastname: Deolindo
authors.forename: Jameel M
authors.initials: JM
authors.lastname: Inal
authors.forename: Marcel I
authors.initials: MI
authors.lastname: Ramirez
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000276:immunology* / Q000378:metabolism*; D004912:Erythrocytes / Q000648:ultrastructure; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D016212:Transforming Growth Factor beta; D050577:Complement C3-C5 Convertases