Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response

Author(s)

Trocoli Torrecilhas, Ana Claudia ^[1] ; Tonelli, Renata Rosito ^[1] ; Pavanelli, Wander Rogerio ^[2] ; da Silva, Joao Santana ^[2] ; Schumacher, Robert Ivan ^[1] ; de Souza, Wanderley ^[3] ; Cunha e Silva, Narcisa ^[3] ; Abrahamsohn, Ises de Almeida ^[4] ; Colli, Walter ^[1] ; Manso Alves, Maria Julia ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05513970 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Imunol, Ribeirao Preto, SP - Brazil

^[3] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, CCS, BR-21949900 Rio De Janeiro - Brazil

^[4] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05513970 Sao Paulo - Brazil

• Document type: Journal article
• Source: Microbes and Infection; v. 11, n. 1, p. 29-39, JAN 2009.
• Web of Science Citations: 84

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 16th day post-infection and 100% on day 20th whereas 20% of untreated animals survived for more than 30 clays. The vesicle-treated animals developed severe heart pathology, with intense inflammatory reaction and higher number of amastigote nests. Analysis of the inflammatory infiltrates 15 days 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. (c) 2008 Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 04/03303-5 - Interaction between Trypanosoma cruzi and host: binders, receptors and conditioners of intracellular development
• Grantee: Maria Julia Manso Alves
• Support Opportunities: Research Projects - Thematic Grants