title: Challenge of chronically infected mice with homologous trypanosoma cruzi parasites enhances the immune response but does not modify cardiopathy: implications for the design of a therapeutic vaccine.
abstract: Chagas disease is a Trypanosoma cruzi-induced zoonosis that has no natural cure. Local damage induced by the parasite and the immune response causes chronic heart and digestive lesions. Efforts to develop a therapeutic vaccine that boosts the immune response to completely clear the parasite are needed because there is no effective treatment for chronically infected patients. In an attempt to modify the host-parasite equilibrium to increase parasite destruction, we analyzed cardiopathy and the immune response in chronically infected mice that were challenged with live homologous parasites. Challenge with a single dose of parasite increased CD4(+) and CD8(+) T cell populations, gamma interferon (IFN-γ) production, and serum-specific IgG levels. However, subpatent parasitemias and cardiac tissue were not affected. Because of the short duration of the immune boost after a single challenge, we next evaluated the impact of four parasite doses, administered 3 weeks apart. At 1 to 2 months after the last dose, the numbers of CD4(+) T cells and IFN-γ-producing CD4(+) memory cells and the CD4(+) T cell proliferative response to T. cruzi antigen were increased in the spleen. The frequency of IFN-γ-producing CD8(+) memory cells in the blood was also increased. However, the sustained challenge did not favor TH1 development; rather, it induced an increase in serum-specific IgG1 levels and mixed TH1/TH2 cytokine production. Moreover, there were no significant changes in cardiac lesions and subpatent parasitemias. In conclusion, we believe that this study may help in elucidating the necessary elements for a successful therapeutic vaccine which may reduce cardiomyopathy in chronically infected human patients.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil. chrisjorquera@gmail.com
authors.forename: Christian Emerson
authors.initials: CE
authors.lastname: Rosas-Jorquera
authors.forename: Luiz Roberto
authors.initials: LR
authors.lastname: Sardinha
authors.forename: Fernando Delgado
authors.initials: FD
authors.lastname: Pretel
authors.forename: André Luis
authors.initials: AL
authors.lastname: Bombeiro
authors.forename: Maria Regina
authors.initials: MR
authors.lastname: D'Império Lima
authors.forename: José Maria
authors.initials: JM
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D005260:Female; D006321:Heart / Q000469:parasitology*; D006790:Host-Parasite Interactions / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009206:Myocardium / Q000473:pathology*; D016052:Protozoan Vaccines / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D007371:Interferon-gamma