Trypanosoma cruzi: parasite antigens sequestered in heart interstitial dendritic cells are related to persisting myocarditis in benznidazole-treated mice.
We investigated whether sequestered Trypanosoma cruzi antigens found in heart interstitial dendritic cells (IDCs) contribute to the residual myocarditis found in mice following treatment with benznidazole, a specific chemotherapeutic drug. IDCs are antigen-presenting cells that are MHC-II-receptor dependent. Swiss mice were divided into two experimental groups: the 1st group was infected with the Colombian strain of T. cruzi, which is resistant to treatment with benznidazole, and the 2nd group was infected with clone 21SF-C 3, which has a medium susceptibility to the drug. Treatment of the Colombian strain group started on the 120th day post-infection and for the 21SF-C3 strain group treatment was started on the 90th day. In both groups, treatment lasted for 90 days. The animals were sacrificed either 150 or 200 days post-treatment. The myocardium was analysed by immunohistochemistry using anti-MAC3, 33D1, CD11b and CD11c monoclonal antibodies for IDCs or anti-T. cruzi purified antibodies. Parasite antigens were expressed on the IDC membranes in both treated and untreated mice. Myocarditis subsided following treatment, evidenced by both histological and morphometrical evaluation. A reduction in the number of IDCs carrying T. cruzi antigens in the treated group indicates that the elimination of parasites influences antigen presentation with concomitant decreases in inflammation. There is a correlation between the presence of T. cruzi antigens in these cells and the chronic focal, residual myocarditis seen in treated mice.
Portella
Renata Siqueira
RS
Laboratório de Chagas Experimental, Autoimunidade e Imunologia Celular, Centro de Pesquisas Gonçalo Moni, Fiocruz, Salvador, BA, Brasil.
Andrade
Sonia G
SG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood; D000953:Antigens, Protozoan / Q000032:analysis* / Q000187:drug effects; D002598:Chagas Cardiomyopathy / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004351:Drug Resistance; D051379:Mice; D009205:Myocarditis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000166:cytology* / Q000276:immunology; D009593:Nitroimidazoles / Q000627:therapeutic use; D013997:Time Factors; D014344:Trypanocidal Agents / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole