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Trypanosoma Cruzi Infection (trypanosoma + cruzi_infection)
Selected AbstractsDepletion of immature B,cells during Trypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathwayEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2005Elina Zuniga Abstract The ability of a microorganism to elicit or evade B,cell responses represents a determinant factor for the final outcome of an infection. Although pathogens may subvert humoral responses at different stages of B,cell development, most studies addressing the impact of an infection on the B,cell compartment have focused on mature B,cells within peripheral lymphoid organs. Herein, we report that a protozoan infection, i.e. a Trypanosoma cruzi infection, induces a marked loss of immature B,cells in the BM, which also compromises recently emigrated B,cells in the periphery. The depletion of BM immature B,cells is associated with an increased rate of apoptosis mediated by a parasite-indirect mechanism in a Fas/FasL-independent fashion. Finally, we demonstrated that myeloid cells play an important role in B,cell depletion, since CD11b+ BM cells from infected mice secrete a product of the cyclooxygenase pathway that eliminates immature B,cells. These results highlight a previously unrecognized maneuver used by a protozoan parasite to disable B,cell generation, limiting host defense and favoring its chronic establishment. [source] Trypanosoma cruzi infection modulates intrathymic contents of extracellular matrix ligands and receptors and alters thymocyte migrationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2003Vinícius Cotta-de-Almeida Abstract Several T cell abnormalities have been described in the course of acute Trypanosoma cruzi infection in mice, including severe effects on the thymus. In the present study, looking at the expression of extracellular matrix ligands in the thymus, we observed that deposits of fibronectin and laminin increased progressively during the course of infection, reaching a maximum at the peak of parasitemia and thymic atrophy. Concomitantly, membrane expression of fibronectin and laminin receptors (VLA-4, VLA-5 and VLA-6) was also enhanced on thymocyte subsets of infected mice. These results correlated with changes in intrathymic thymocyte migration ability during the acute phase of infection, when a higher fibronectin-dependent transmigratory activity of CD4+CD8+ thymocytes was observed. Strikingly, we detected higher frequency of immature and high VLA-expressing CD4+CD8+ T cells in the peripheral lymphoid organs of infected mice at thepeak of parasitemia. These cells seemed to be thymus dependent, since significantly lower amounts of them were found in thymectomized mice, and some of them carry "prohibited" V, segments of the TCR. Our data suggest an imbalance in the intrathymic cell trafficking following acute T. cruzi infection, likely due to dysregulated extracellular matrix-dependent interactions. [source] Evidence for a perforin-mediated mechanism controlling cardiac inflammation in Trypanosoma cruzi infectionINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2002ANDREA HENRIQUES-PONS Summary. ,CD8+ T lymphocytes are considered an important cell population involved in the control of parasitaemia and mortality after Trypanosoma cruzi infection. However, despite recent developments in this field, the mechanism whereby this control is exerted is still not completely understood. Here we have used perforin knockout (,/,) mice infected with Y strain T. cruzi in order to evaluate specifically the participation of the perforin-based cytotoxic pathway in the destruction of cardiomyocytes, cellular inflammatory infiltration, and control of parasitaemia and mortality. We observed that although parasitaemia was equivalent in perforin (+/+) and (,/,) groups, survival rate and spontaneous physical performance were significantly lower in the perforin deficient mice. The cardiac inflammatory cell infiltration, mostly composed of CD8+ cells, was more evident in perforin (,/,) mice. Ultrastructural and immunofluorescence analysis, as well as plasma creatine kinase activity, revealed cardiomyocyte damage and necrosis, more evident in perforin (,/,) mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays performed in heart samples revealed similar and modest levels of apoptosis in both perforin (+/+) and (,/,) mice. These results indicate that perforin does not play a pivotal role in the control of parasitaemia and direct lysis of cardiomyocytes, but seems to be an important molecule involved in the control of cardiac inflammation and pathology induced by a highly virulent strain of T. cruzi. [source] Enhancement of natural killer (NK) cell cytotoxicity and induction of NK cell-derived interferon-gamma (IFN- ,) display different kinetics during experimental infection with Trypanosoma cruziCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2000C. Une Early immunological activation involves an initial phase of cytokine activity and involvement of cell types such as NK cells. Such early immune responses are often decisive in resolution of microbial infection. NK cells reduce parasitaemia and enhance survival in experimental Trypanosoma cruzi infection, although the nature of these protective effects is not well understood. In this study, a detailed analysis of innate cytokine induction in the absence and presence of NK cells during the first 8 days of infection was performed. Following intraperitoneal infection with a high dose of parasites, reverse transcriptase-polymerase chain reaction showed that splenic mRNA for IFN- , appeared as a peak 24 h after infection and then reappeared 2,3 days later. In NK-depleted animals the first peak of IFN- , was absent and the second wave was slightly delayed. mRNA for IL-12 and tumour necrosis factor-alpha (TNF- ,) as well as IFN- , protein in serum was only recorded 24 h after infection, at the same time as the IFN- , peak. NK depletion resulted in a small decrease of IL-12 mRNA levels, whereas TNF- , and IFN- , were not affected. NK cytotoxicity remained elevated throughout the 8 days and thus did not parallel the expression of IFN- , production by NK cells. We conclude that NK cell cytokine production and cytolytic activity play different roles in response to challenge with T. cruzi. [source] Differential regulation of nitric oxide synthase isoforms in experimental acute Chagasic cardiomyopathyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2000B. Chandrasekar We have previously demonstrated induction and high level expression of IL-1,, IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial depressive effects of these cytokines are mediated in part by the induction of nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of peroxynitrite. In this study we investigated the expression, activity and localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of oxidative stress), and peroxynitrite in rats at 1·5, 5, 10 and 15 days after infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate and number of amastigote nests increased over the course of infection. A significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2 enzyme activity was observed at all time points in the infected compared with uninfected animals. The enzyme activity of constitutive NOS, tissue malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after infection. The protein levels of the NOS isoforms paralleled their mRNA expression. While no positive nitrotyrosine immunoreactivity was detected in control myocardium, its levels increased in infected animals over time. Thus, by 1·5 days post-infection, when no parasite or immune cell infiltration could be detected, the myocardium expressed high levels of NOS and NO metabolites. Nevertheless, the early production of NO in the myocardium was not sufficient to clear the parasites. [source] | ||||||||||