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ABSTRACTCutaneous leishmaniasis (CL) caused by Leishmania braziliensisis characterized by a strong Th1 response that leads to skin lesion development. In areas where L. braziliensistransmission is endemic, up to 15% of healthy subjects have tested positive for delayed-type hypersensitivity to soluble leishmania antigen (SLA) and are considered to have subclinical (SC) infection. SC subjects produce less gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) than do CL patients, but they are able to control the infection. The aim of this study was to characterized the role of CD8+T cells in SC infection and in CL. Peripheral blood mononuclear cells (PBMC) were stimulated with SLA to determine the frequencies of CD4+IFN-γ+and CD8+IFN-γ+T cells. Monocytes from PBMC were infected with L. braziliensisand cocultured with CD8+T cells, and the frequencies of infected monocytes and levels of cytotoxicity markers, target cell apoptosis, and granzyme B were determined. The frequency of CD8+IFN-γ+cells after SLA stimulation was higher for SC individuals than for CL patients. The frequency of infected monocytes in SC cells was lower than that in CL cells. CL CD8+T cells induced more apoptosis of infected monocytes than did SC CD8+T cells. Granzyme B production in CD8+T cells was higher in CL than in SC cells. While the use of a granzyme B inhibitor decreased the number of apoptotic cells in the CL group, the use of z-VAD-FMK had no effect on the frequency of these cells. These results suggest that CL CD8+T cells are more cytotoxic and may be involved in pathology.

ABSTRACTIn areas where schistosomiasis is endemic, a negative correlation is observed between atopy and helminth infection, associated with a low prevalence of asthma. We investigated whether Schistosoma mansoniinfection or injection of parasite eggs can modulate airway allergic inflammation in mice, examining the mechanisms of such regulation. We infected BALB/c mice with 30 S. mansonicercariae or intraperitoneally injected 2,500 schistosome eggs, and experimental asthma was induced by ovalbumin (OVA). The number of eosinophils in bronchoalveolar lavage fluid was higher in the asthmatic group than in asthmatic mice infected with S. mansonior treated with parasite eggs. Reduced Th2 cytokine production, characterized by lower levels of interleukin-4 (IL-4), IL-5, and immunoglobulin E, was observed in both S. mansoni-treated groups compared to the asthmatic group. There was a reduction in the number of inflammatory cells in lungs of S. mansoni-infected and egg-treated mice, demonstrating that both S. mansoniinfection and the egg treatment modulated the lung inflammatory response to OVA. Only allergic animals that were treated with parasite eggs had increased numbers of CD4+CD25+Foxp3+T cells and increased levels of IL-10 and decreased production of CCL2, CCL3, and CCL5 in the lungs compared to the asthmatic group. Neutralization of IL-10 receptor or depletion of CD25+T cells in vivo confirmed the critical role of CD4+CD25+Foxp3+regulatory T cells in experimental asthma modulation independent of IL-10.

In areas where schistosomiasis is endemic, a negative correlation is observed between atopy and helminth infection, associated with a low prevalence of asthma. We investigated whether Schistosoma mansoni infection or injection of parasite eggs can modulate airway allergic inflammation in mice, examining the mechanisms of such regulation. We infected BALB/c mice with 30 S. mansoni cercariae or intraperitoneally injected 2,500 schistosome eggs, and experimental asthma was induced by ovalbumin (OVA). The number of eosinophils in bronchoalveolar lavage fluid was higher in the asthmatic group than in asthmatic mice infected with S. mansoni or treated with parasite eggs. Reduced Th2 cytokine production, characterized by lower levels of interleukin-4 (IL-4), IL-5, and immunoglobulin E, was observed in both S. mansoni-treated groups compared to the asthmatic group. There was a reduction in the number of inflammatory cells in lungs of S. mansoni-infected and egg-treated mice, demonstrating that both S. mansoni infection and the egg treatment modulated the lung inflammatory response to OVA. Only allergic animals that were treated with parasite eggs had increased numbers of CD4+CD25+Foxp3+T cells and increased levels of IL-10 and decreased production of CCL2, CCL3, and CCL5 in the lungs compared to the asthmatic group. Neutralization of IL-10 receptor or depletion of CD25+T cells in vivo confirmed the critical role of CD4+CD25+Foxp3+regulatory T cells in experimental asthma modulation independent of IL-10.

ABSTRACTThe objective of this study was to evaluate the role of cytokines in hepatic fibrosis in the prehepatosplenic and early hepatosplenic stages of schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography of 94 patients. Immunological evaluation was performed by the measurement of secreted cytokines (interleukin-5 [IL-5], IL-10, IL-13, gamma interferon, tumor necrosis factor alpha, and transforming growth factor β) in peripheral blood mononuclear cells (PBMC) stimulated by Schistosoma mansoniantigens. Significantly, higher levels of IL-5, IL-10, and IL-13 were found in supernatants of soluble egg antigen-stimulated PBMC from subjects with degree III hepatic fibrosis compared to patients with degree I or II fibrosis. Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for 1 year following initial assessment and developed more serious fibrosis during this period. The data suggest a role for type 2 cytokines in hepatic fibrosis in human schistosomiasis mansoni.

ABSTRACTTo determine the naturally occurring immunological responses to theSchistosoma mansoniantigens paramyosin, IrV-5, Sm-23 (MAP-3), and triose phosphate isomerase (MAP-4), a total of 119 subjects from an area of endemicity for schistosomiasis, including “resistant” subjects (n= 17) were evaluated. Specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgA levels for each of the antigens and the cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC) were determined. Although all the subjects had a high degree of contaminated water exposure, their infection levels were variable (0 to 1,128 eggs/g of stool). There were direct correlations between infection levels and levels of SWAP- and paramyosin-specific IgG1 and IgG4 (P< 0.05). However, an inverse correlation between infection levels and specific IgG2 to IrV-5 (P< 0.01) was observed. The evaluation of the cytokine profile (interleukin 5 [IL-5], IL-10, gamma interferon [IFN-γ], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-γ levels in PBMC supernatants stimulated with paramyosin (P< 0.05) and IrV-5 (P< 0.01). Additionally, inverse correlations between the degree of infection and IL-5 levels in MAP-3- and MAP-4-stimulated PBMC supernatants (P< 0.01) were found. Logistic regression analysis was performed to adjust the results of cytokine profile by age. IL-5 production in MAP-3-stimulated PBMC supernatants was associated with lower infection levels (odds ratio = 11.2 [95% confidence interval, 2.7 to 45.8]).