Schistosoma mansoni Antigens Modulate Experimental Allergic Asthma in a Murine Model: a Major Role for CD4 ⁺ CD25 ⁺ Foxp3 ⁺ T Cells Independent of Interleukin-10

Abstract

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...

Strongyloides ratti Infection Induces Expansion of Foxp3+ Regulatory T Cells That Interfere with Immune Response and Parasite Clearance in BALB/c Mice

“…Interestingly, the suppression of immune responses to unrelated Ags that is often observed upon helminth infection was also shown to be associated with Tregs in some studies. Using models of adoptive transfer or depletion by anti-CD25 mAb, Tregs have been identified as one of the helminth-induced cell populations responsible for silencing the pathology in OVA-induced asthma (58)(59)(60)(61) or counteracting the protective immune response to Plasmodium yoelii in a coinfection model (62).…”

Pneumococcal Components Induce Regulatory T Cells That Attenuate the Development of Allergic Airways Disease by Deviating and Suppressing the Immune Response to Allergen

“…4G). Once recruited, CCR7 + cells migrate out of the lung and into the lymph nodes (19,20). At the same time, there was an increase in Treg-promoting factors (IL-2 and TGF-b).…”

Association between allergic responses and Schistosoma mansoni infection in residents in a low-endemic setting in Brazil

“…Helminth infections and allergic diseases are both associated with Th2 cytokines and high levels of immunoglobulin E (IgE) and eosinophilia. Although the two conditions appear to involve similar immune responses, a negative correlation has been demonstrated between helminth infection and allergic diseases 13 . Many epidemiologists investigating the increasing prevalence of allergic diseases subscribe to the hygiene hypothesis 14 , which asserts that the lack of exposure to infectious agents and parasites, improvements in hygiene and the use of vaccines and antibiotics (especially in developed countries) can compromise the ability of the immune system to respond adequately to certain challenges, conceivably due to an imbalance between the Th1 and Th2 cell-mediated immune responses 15 .…”