Trypanosoma cruzi: Tc52 released protein-induced increased expression of nitric oxide synthase and nitric oxide production by macrophages.
Trypanosoma cruzi target molecules that might regulate the host immune responses have not yet been fully identified. In the present study, we demonstrate that the parasite-released molecule (Tc52) was able to synergize with IFN-gamma to stimulate nitric oxide production by macrophages. This synergistic effect was also observed at the level of inducible nitric oxide synthase gene expression. Furthermore, Tc52 was also shown to induce gene expression for IL-1alpha, IL-12, and IL-10. Moreover, the combination of Tc52 and IFN-gamma down-regulates IL-1alpha and IL-10 gene expression, but not IL-12. Isotype profiles and Tc52 or anti-CD3-induced T cell proliferation were also analyzed, indicating that active immunization with Tc52 partially relieves the immunosuppression observed during the acute phase of the disease. Moreover, under conditions of experimental infection, the Tc52 appears immunologically silent, failing to elicit Ab response and lymphocyte proliferation during the initial acute phase infection. Following active immunization, Tc52 was capable of stimulating T cell proliferation and Ab production with a predominance of IgG1, IgG2a, IgG2b, IgG3, and to a lesser extent IgA. Taken together, these results demonstrate that T. cruzi Tc52-released Ag could be involved in the immunoregulatory processes. The immune response against Tc52 that appears late in the T. cruzi infection may play a role in the modulation of its biological function(s).
Fernandez-Gomez
R
R
Facultad De Ciencias Quimicas Universidad Autonoma de Zacatecas, Cuauhtemoc, Guadalupe, Mexico.
Esteban
S
S
Gomez-Corvera
R
R
Zoulika
K
K
Ouaissi
A
A
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011485:Protein Binding / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
C097550:52-kDa protein, Trypanosoma cruzi; D000913:Antibodies, Protozoan; D016207:Cytokines; D015800:Protozoan Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse