title: Trypanosoma cruzi carrying a targeted deletion of a Tc52 protein-encoding allele elicits attenuated Chagas' disease in mice.
abstract: The intracellular protozoan parasite Trypanosoma cruzi is the etiological agent of Chagas' disease. We have previously characterized a T. cruzi virulence factor named Tc52 sharing structural and functional properties with the thioredoxin and glutaredoxin protein family. Single mutant parasite clones (Tc52(+/-)) exhibiting low virulence in vitro and in vivo were obtained by targeted Tc52 gene replacement. In this report, we have extended our study to analyze the immune response and the disease phenotype in Tc52(+/-)-infected BALB/c mice, during the acute and chronic phases of the disease. Significantly lower parasitemia were found in Tc52(+/-)-infected mice, as compared to wild-type parasite (WT)-infected ones. However, the expansion of all classes of lymphocytes and macrophages was similar for both clones. Furthermore, except for IgG2b levels which were higher in the case of WT-infected mice, all classes of Ig presented no significant difference for WT and Tc52(+/-)-infected animals. Interestingly, a lack of suppression of IL-2 production and of T-cell proliferation inhibition was observed in the case of spleen cells from Tc52(+/-)-infected mice. Finally, the pattern of inflammation process was different and characterized as diffused in the case of Tc52(+/-)-infected mice, or presenting numerous foci in the case of WT-infected mice. Localization of the Tc52 protein in tissue sections and infected heart cell primary cultures by immunofluorescence and immunogold labeling, respectively, revealed the presence of Tc52 at the amastigote surface and associated to aggregates within host cell vesicles. Taken together, these results reinforce the notion of Tc52 being a virulence factor playing a role in the phenotype of the immune response associated to the infection and on the course of the disease.
authors.affiliation: IRD UR 008 Pathogénie des Trypanosomatidae, Centre IRD de Montpellier, 911 Avenue Agropolis, BP 5045, 34032 Montpellier Cedex, France.
authors.forename: Edwin
authors.initials: E
authors.lastname: Garzón
authors.forename: Margarida Coutinho
authors.initials: MC
authors.lastname: Borges
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
authors.forename: Valeria
authors.initials: V
authors.lastname: Nacife
authors.forename: Maria de Nazareth
authors.initials: Mde N
authors.lastname: Meirelles
authors.forename: Eliane
authors.initials: E
authors.lastname: Guilvard
authors.forename: Marie France
authors.initials: MF
authors.lastname: Bosseno
authors.forename: Angel Gustavo
authors.initials: AG
authors.lastname: Guevara
authors.forename: Simone Frédérique
authors.initials: SF
authors.lastname: Brenière
authors.forename: Ali
authors.initials: A
authors.lastname: Ouaissi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D017209:Apoptosis; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D018390:Gene Targeting; D006321:Heart / Q000469:parasitology; D007136:Immunoglobulins / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000737:chemistry / Q000469:parasitology / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D015800:Protozoan Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology
chemical_list: C097550:52-kDa protein, Trypanosoma cruzi; D000913:Antibodies, Protozoan; D016207:Cytokines; D007136:Immunoglobulins; D015800:Protozoan Proteins; D007371:Interferon-gamma