Schistosomes Induce Regulatory Features in Human and Mouse CD1d^hi B Cells: Inhibition of Allergic Inflammation by IL-10 and Regulatory T Cells

<div><p>Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, <em>Schistosoma mansoni</em>-mediated protection against experimental ovalbumin-induced allergic airway inflammation (AAI) was shown to be specifically dependent on IL-10-producing B cells. To study the organs involved, we transferred B cells from lungs, mesenteric lymph nodes or spleen of OVA-infected mice to recipient OVA-sensitized mice, and showed that both lung and splenic B cells reduced AAI, but only splenic B cells in an IL-10-dependent manner. Although splenic B cell protection was accompanied by elevated levels of pulmonary FoxP3⁺ regulatory T cells, <em>in vivo</em> ablation of FoxP3⁺ T cells only moderately restored AAI, indicating an important role for the direct suppressory effect of regulatory B cells. Splenic marginal zone CD1d⁺ B cells proved to be the responsible splenic B cell subset as they produced high levels of IL-10 and induced FoxP3⁺ T cells <em>in vitro</em>. Indeed, transfer of CD1d⁺ MZ-depleted splenic B cells from infected mice restored AAI. Markedly, we found a similarly elevated population of CD1d^hi B cells in peripheral blood of <em>Schistosoma haematobium</em>-infected Gabonese children compared to uninfected children and these cells produced elevated levels of IL-10. Importantly, the number of IL-10-producing CD1d^hi B cells was reduced after anti-schistosome treatment. This study points out that in both mice and men schistosomes have the capacity to drive the development of IL-10-producing regulatory CD1d^hi B cells and furthermore, these are instrumental in reducing experimental allergic inflammation in mice.</p>