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

van der Vlugt LE, Labuda LA, Ozir-Fazalalikhan A, Lievers E, Gloudemans AK, Liu KY, Barr TA, Sparwasser T, Boon L, Ngoa UA, Feugap EN, Adegnika AA, Kremsner PG, Gray D, Yazdanbakhsh M, Smits HH - PLoS ONE (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.

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.

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MZ B cells are important in the protection against AAI.(A) Mock-depleted splenic and the MZ-depleted B cells were injected in OVA-sensitized recipient mice. After challenge, total BAL cell count and the number of BAL eosinophils (B) and the percentage of CD4+CD25+FoxP3+ T cells in the lungs (C) was measured. Figure is representative of two independent experiments, consisting of five mice per group.
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pone-0030883-g005: MZ B cells are important in the protection against AAI.(A) Mock-depleted splenic and the MZ-depleted B cells were injected in OVA-sensitized recipient mice. After challenge, total BAL cell count and the number of BAL eosinophils (B) and the percentage of CD4+CD25+FoxP3+ T cells in the lungs (C) was measured. Figure is representative of two independent experiments, consisting of five mice per group.

Mentions: Next, the contribution of the MZ B cells in vivo was investigated by depletion of the CD21hi cells from total splenic B cells of OVA-uninfected or OVA-infected mice by indirect magnetic labeling (Fig. 5A). The transfer of mock-treated B cells from OVA-infected mice resulted in a decrease in total BAL cell count and eosinophilia (Fig. 5B), as observed before. Importantly, the transfer of CD21+-depleted B cells restored the severity of AAI and the induction of pulmonary FoxP3+ Treg cells was lost (Fig. 5C), confirming the significance of MZ B cells in protection against AAI in vivo.


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

van der Vlugt LE, Labuda LA, Ozir-Fazalalikhan A, Lievers E, Gloudemans AK, Liu KY, Barr TA, Sparwasser T, Boon L, Ngoa UA, Feugap EN, Adegnika AA, Kremsner PG, Gray D, Yazdanbakhsh M, Smits HH - PLoS ONE (2012)

MZ B cells are important in the protection against AAI.(A) Mock-depleted splenic and the MZ-depleted B cells were injected in OVA-sensitized recipient mice. After challenge, total BAL cell count and the number of BAL eosinophils (B) and the percentage of CD4+CD25+FoxP3+ T cells in the lungs (C) was measured. Figure is representative of two independent experiments, consisting of five mice per group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3275567&req=5

pone-0030883-g005: MZ B cells are important in the protection against AAI.(A) Mock-depleted splenic and the MZ-depleted B cells were injected in OVA-sensitized recipient mice. After challenge, total BAL cell count and the number of BAL eosinophils (B) and the percentage of CD4+CD25+FoxP3+ T cells in the lungs (C) was measured. Figure is representative of two independent experiments, consisting of five mice per group.
Mentions: Next, the contribution of the MZ B cells in vivo was investigated by depletion of the CD21hi cells from total splenic B cells of OVA-uninfected or OVA-infected mice by indirect magnetic labeling (Fig. 5A). The transfer of mock-treated B cells from OVA-infected mice resulted in a decrease in total BAL cell count and eosinophilia (Fig. 5B), as observed before. Importantly, the transfer of CD21+-depleted B cells restored the severity of AAI and the induction of pulmonary FoxP3+ Treg cells was lost (Fig. 5C), confirming the significance of MZ B cells in protection against AAI in vivo.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.

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.

Show MeSH
Related in: MedlinePlus