Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response.
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.
Trocoli Torrecilhas
Ana Claudia
AC
Departamento de Bioquímica, Instituto de Química, USP, Av. Lineu Prestes, 748, 05508-900 São Paulo, SP, Brazil.
Tonelli
Renata Rosito
RR
Pavanelli
Wander Rogério
WR
da Silva
João Santana
JS
Schumacher
Robert Ivan
RI
de Souza
Wanderley
W
E Silva
Narcisa Cunha
NC
de Almeida Abrahamsohn
Ises
I
Colli
Walter
W
Manso Alves
Maria Júlia
MJ
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
D006023:Glycoproteins; D016753:Interleukin-10; D015847:Interleukin-4; C069715:trans-sialidase; D009439:Neuraminidase