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Schistosomes Induce Regulatory Features in Human and Mouse CD1dhi B Cells: Inhibition of Allergic Inflammation by IL-10 and Regulatory T Cells

By PLoS ONE • on February 9, 2012

by Luciën E. P. M. van der Vlugt, Lucja A. Labuda, Arifa Ozir-Fazalalikhan, Ellen Lievers, Anouk K. Gloudemans, Kit-Yeng Liu, Tom A. Barr, Tim Sparwasser, Louis Boon, Ulysse Ateba Ngoa, Eliane Ngoune Feugap, Ayola A. Adegnika, Peter G. Kremsner, David Gray, Maria Yazdanbakhsh, Hermelijn H. Smits

Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, Schistosoma mansoni-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, in vivo 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 in vitro. 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 Schistosoma haematobium-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.