title: 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.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Luciën E P M
authors.initials: LE
authors.lastname: van der Vlugt
authors.forename: Lucja A
authors.initials: LA
authors.lastname: Labuda
authors.forename: Arifa
authors.initials: A
authors.lastname: Ozir-Fazalalikhan
authors.forename: Ellen
authors.initials: E
authors.lastname: Lievers
authors.forename: Anouk K
authors.initials: AK
authors.lastname: Gloudemans
authors.forename: Kit-Yeng
authors.initials: KY
authors.lastname: Liu
authors.forename: Tom A
authors.initials: TA
authors.lastname: Barr
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Ulysse Ateba
authors.initials: UA
authors.lastname: Ngoa
authors.forename: Eliane Ngoune
authors.initials: EN
authors.lastname: Feugap
authors.forename: Ayola A
authors.initials: AA
authors.lastname: Adegnika
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: David
authors.initials: D
authors.lastname: Gray
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.forename: Hermelijn H
authors.initials: HH
authors.lastname: Smits
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D002648:Child; D005681:Gabon / Q000453:epidemiology; D006376:Helminths; D006801:Humans; D006967:Hypersensitivity / Q000469:parasitology / Q000473:pathology*; D007249:Inflammation / Q000276:immunology / Q000469:parasitology; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012547:Schistosoma / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000469:parasitology
chemical_list: D055610:Antigens, CD1d; C508609:IL10 protein, human; C556062:IL10 protein, mouse; D016753:Interleukin-10