title: Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response.
abstract: Trypanosoma cruzi trypomastigotes continuously shed into the medium plasma membrane fragments sealed as vesicles enriched in glycoproteins of the gp85 and trans-sialidase (TS) superfamily and alpha-galactosyl-containing glycoconjugates. Injection of a vesicle fraction into BALB/c mice prior to T. cruzi infection led to 40% of deaths on the 16thday post-infection and 100% on day 20th whereas 20% of untreated animals survived for more than 30days. The vesicle-treated animals developed severe heart pathology, with intense inflammatory reaction and higher number of amastigote nests. Analysis of the inflammatory infiltrates 15days after infection showed predominance of TCD4(+) lymphocytes and macrophages, but not of TCD8(+) cells, as well as a decrease of areas labeled with anti-iNOS antibodies as compared to the control. Higher levels of IL-4 and IL-10 mRNAs were found in the hearts and higher IL-10 and lower NO levels in splenocytes of vesicles pretreated animals. Treatment of mice with neutralizing anti-IL-10 or anti-IL-4 antibodies precluded the effects of pre-inoculation of membrane vesicles on infection. These results indicate that T. cruzi shed membrane components increase tissue parasitism and inflammation by stimulation of IL-4 and IL-10 synthesis and thus may play a central role in the pathogenesis of Chagas' disease acute phase.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, USP, Av. Lineu Prestes, 748, 05508-900 São Paulo, SP, Brazil.
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Trocoli Torrecilhas
authors.forename: Renata Rosito
authors.initials: RR
authors.lastname: Tonelli
authors.forename: Wander Rogério
authors.initials: WR
authors.lastname: Pavanelli
authors.forename: João Santana
authors.initials: JS
authors.lastname: da Silva
authors.forename: Robert Ivan
authors.initials: RI
authors.lastname: Schumacher
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
authors.forename: Narcisa Cunha
authors.initials: NC
authors.lastname: E Silva
authors.forename: Ises
authors.initials: I
authors.lastname: de Almeida Abrahamsohn
authors.forename: Walter
authors.initials: W
authors.lastname: Colli
authors.forename: Maria Júlia
authors.initials: MJ
authors.lastname: Manso Alves
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology*; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000401:mortality / Q000469:parasitology / Q000503:physiopathology; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006321:Heart / Q000469:parasitology*; D007249:Inflammation / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D009439:Neuraminidase / Q000032:analysis; D014349:Trypanosoma cruzi / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D006023:Glycoproteins; D016753:Interleukin-10; D015847:Interleukin-4; C069715:trans-sialidase; D009439:Neuraminidase