Schistosomes induce regulatory features in human and mouse CD1d(hi) B cells: inhibition of allergic inflammation by IL-10 and regulatory T cells.

Abstract

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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 7 Issue 2 Pg. e30883 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22347409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD1d
• IL10 protein, human
• IL10 protein, mouse
• Interleukin-10

Topics

• Animals
• Antigens, CD1d (immunology)
• B-Lymphocytes (immunology, parasitology)
• Child
• Gabon (epidemiology)
• Helminths
• Humans
• Hypersensitivity (parasitology, pathology)
• Inflammation (immunology, parasitology)
• Interleukin-10 (deficiency, immunology)
• Mice
• Mice, Knockout
• Schistosoma (immunology)
• T-Lymphocytes, Regulatory (immunology, parasitology)