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.The prevalence of allergic diseases such as asthma has increased markedly over the past few decades (5). The immune response to allergens is characterized by eosinophilic inflammation of the airways, airway hyperreactivity, and immunoglobulin E (IgE) production by B cells (39). The immune etiology of asthma is complex. Genetic and immunological analyses of atopic individuals have revealed that Th2 cytokines are usually associated with allergies (23, 25). Furthermore, Th2 cells which produce interleukin-4 (IL-4), IL-5, and IL-13 mediate the inflammatory reaction in the lung. Production of IL-5 increases differentiation, recruitment, and survival of eosinophils and therefore plays an important role in the development of pulmonary eosinophilia during allergic disorders (26). Moreover, IL-13 is important for IgE production, mucus hyperplasia, and eosinophilia (34). The levels of these cytokines are higher in allergic patients and play a direct role in the inflammatory response.It has been suggested that people in developing countries suffer less from allergic disease than those who live in industrialized countries because the former are frequently exposed to bacteria and helminth infections associated with poverty and lack of basic sanitary conditions (21). Both helminth infections and allergic diseases are associated with Th2 cytokines and high levels of IgE and eosinophilia. Though they appear to have similar immune responses, a negative correlation between helminth infection and allergic disease has been obse...

BackgroundRecombinant proteins expressed in Escherichia coli vectors are generally contaminated with endotoxin. In this study, we evaluated the ability of Polymyxin B to neutralize the effect of LPS present as contaminant on Schistosoma mansoni recombinant proteins produced in E. coli in inducing TNF-α and IL-10. Peripheral blood mononuclear cells from individuals chronically infected with S. mansoni were stimulated in vitro with recombinant Sm22.6, Sm14 and P24 antigens (10 μg/mL) in the presence of Polymyxin B (10 μg/mL).ResultsThe levels of cytokines were measured using ELISA. There was greater than 90 % reduction (p < 0.05) in the levels of TNF-α and IL-10 when Polymyxin B was added to the cultures stimulated with LPS. In cultures stimulated with S. mansoni recombinant proteins in the presence of Polymyxin B, a reduction in the levels of TNF-α and IL-10 was also observed. However, the percentage of reduction was lower when compared to the cultures stimulated with LPS, probably because these proteins are able to induce the production of these cytokines by themselves.ConclusionThis study showed that Polymyxin B was able to neutralize the effect of endotoxin, as contaminant in S. mansoni recombinant antigens produced in E. coli, in inducing TNF-α and IL-10 production.

SummarySchistosoma mansoni infection has been associated with protection against allergies. The mechanisms underlying this association may involve regulatory cells and cytokines. We evaluated the immune response induced by the S. mansoni antigens Sm22·6, PIII and Sm29 in a murine model of ovalbumin (OVA)-induced airway inflammation. BALB/c mice were sensitized with subcutaneously injected OVA-alum and challenged with aerolized OVA. Mice were given three doses of the different S. mansoni antigens. Lung histopathology, cellularity of bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in lung were evaluated. Immunoglobulin (Ig)E levels in serum and cytokines in BAL were also measured. Additionally, we evaluated the frequency of CD4+ forkhead box P3 (FoxP3) + T cells in cultures stimulated with OVA and the expression of interleukin (IL)-10 by these cells. The number of total cells and eosinophils in BAL and the levels of OVA-specific IgE were reduced in the immunized mice. Also, the levels of IL-4 and IL-5 in the BAL of mice immunized with PIII and Sm22·6 were decreased, while the levels of IL-10 were higher in mice immunized with Sm22·6 compared to the nonimmunized mice. The frequency of CD4 + FoxP3 + T cells was higher in the groups of mice who received Sm22·6, Sm29 and PIII, being the expression of IL-10 by these cells only higher in mice immunized with Sm22·6. We concluded that the S. mansoni antigens used in this study are able to downmodulate allergic inflammatory mediators in a murine model of airway inflammation and that the CD4 + FoxP3 + T cells, even in the absence of IL-10 expression, might play an important role in this process.

No abstract