Trypanosoma cruzi carrying a targeted deletion of a Tc52 protein-encoding allele elicits attenuated Chagas' disease in mice
| Autor: | Edwin Garzón, Margarida Coutinho Borges, Anabela Cordeiro-da-Silva, Valeria Nacife, Maria de Nazareth Meirelles, Eliane Guilvard, Marie France Bosseno, Angel Gustavo Guevara, Simone Frédérique Brenière, Ali Ouaissi |
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| Rok vydání: | 2003 |
| Předmět: |
Chagas disease
Trypanosoma cruzi Immunology Protozoan Proteins Antibodies Protozoan Immunoglobulins Virulence Apoptosis Enzyme-Linked Immunosorbent Assay Spleen Parasitemia PHENOTYPE Virulence factor Interferon-gamma Mice Immune system SOURIS medicine Animals Immunology and Allergy Chagas Disease PARASITE Muscle Skeletal Amastigote MUTATION Cells Cultured IMMUNITE Mice Inbred BALB C biology Myocardium Heart medicine.disease biology.organism_classification Virology Molecular biology medicine.anatomical_structure MALADIE DE CHAGAS Gene Targeting VIRULENCE Cytokines |
| Zdroj: | Immunology Letters. 89:67-80 |
| ISSN: | 0165-2478 |
| Popis: | 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 ( Tc 52 +/− ) exhibiting low virulence in vitro and in vivo were obtained by targeted Tc 52 gene replacement. In this report, we have extended our study to analyze the immune response and the disease phenotype in Tc 52 +/− -infected BALB/c mice, during the acute and chronic phases of the disease. Significantly lower parasitemia were found in Tc 52 +/− -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 Tc 52 +/− -infected mice. Finally, the pattern of inflammation process was different and characterized as diffused in the case of Tc 52 +/− -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. |
| Databáze: | OpenAIRE |
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