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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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IL-10 production by B cells from different organs during chronic schistosomiasis and their role in protection against AAI.(A) WT mice were treated as in Fig. 1A. Splenic, pulmonary or mesenteric B cells (1×105) were isolated and cultured in the presence of SEA (20 µg/ml) for five days. IL-10 production was measured using ELISA and medium value was subtracted. (B) OVA-sensitized recipient mice received 5×106 B cells from different organs. After challenge, BAL cell numbers and eosinophils were determined (C) BAL numbers and eosinophilia of mice that received 250 µg isotype control or anti-IL-10R abs per mouse one day before the adoptive transfer. (D) The percentage of CD4+CD25+FoxP3+ Treg cells was determined in the lungs of recipient mice. Each graph represents three independent experiments, consisting of five mice per group.
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pone-0030883-g002: IL-10 production by B cells from different organs during chronic schistosomiasis and their role in protection against AAI.(A) WT mice were treated as in Fig. 1A. Splenic, pulmonary or mesenteric B cells (1×105) were isolated and cultured in the presence of SEA (20 µg/ml) for five days. IL-10 production was measured using ELISA and medium value was subtracted. (B) OVA-sensitized recipient mice received 5×106 B cells from different organs. After challenge, BAL cell numbers and eosinophils were determined (C) BAL numbers and eosinophilia of mice that received 250 µg isotype control or anti-IL-10R abs per mouse one day before the adoptive transfer. (D) The percentage of CD4+CD25+FoxP3+ Treg cells was determined in the lungs of recipient mice. Each graph represents three independent experiments, consisting of five mice per group.

Mentions: In order to identify the dominant organ with IL-10-producing B cells during infection, we isolated B cells from organs that have previously been described to harbor regulatory B cells (spleen), drain schistosome infection sites (mesenteric lymph nodes, MLN) or are the effector site where allergic inflammation is found (lung). Both pulmonary and splenic B cells, but not mesenteric B cells, from chronically-infected mice were able to produce IL-10 upon soluble egg antigen (SEA) stimulation, with highest production by splenic B cells (Fig. 2A). To study the suppressive activity of isolated B cells from different organs in downmodulating AAI, we adoptively transferred CD19+ B cells from OVA-infected mice into OVA-sensitized recipient mice. AAI was reduced by pulmonary or splenic but not by mesenteric B cells (Fig. 2B). Interestingly, the protective effect of the transfer of splenic B cells, but not of pulmonary B cells, was abolished by administering a blocking IL-10 receptor antibody (Fig. 2C). Furthermore, we observed increased percentages of CD4+CD25+FoxP3+ T cells in the lungs of recipient mice, but only after administering splenic B cells (Fig. 2D). This data indicate that pulmonary B cells can drive IL-10 and Treg cell-independent protection against eosinophilic AAI, while splenic B cells protect via an IL-10-dependent mechanism and enhance local Treg cell numbers in the lungs.


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)

IL-10 production by B cells from different organs during chronic schistosomiasis and their role in protection against AAI.(A) WT mice were treated as in Fig. 1A. Splenic, pulmonary or mesenteric B cells (1×105) were isolated and cultured in the presence of SEA (20 µg/ml) for five days. IL-10 production was measured using ELISA and medium value was subtracted. (B) OVA-sensitized recipient mice received 5×106 B cells from different organs. After challenge, BAL cell numbers and eosinophils were determined (C) BAL numbers and eosinophilia of mice that received 250 µg isotype control or anti-IL-10R abs per mouse one day before the adoptive transfer. (D) The percentage of CD4+CD25+FoxP3+ Treg cells was determined in the lungs of recipient mice. Each graph represents three 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-g002: IL-10 production by B cells from different organs during chronic schistosomiasis and their role in protection against AAI.(A) WT mice were treated as in Fig. 1A. Splenic, pulmonary or mesenteric B cells (1×105) were isolated and cultured in the presence of SEA (20 µg/ml) for five days. IL-10 production was measured using ELISA and medium value was subtracted. (B) OVA-sensitized recipient mice received 5×106 B cells from different organs. After challenge, BAL cell numbers and eosinophils were determined (C) BAL numbers and eosinophilia of mice that received 250 µg isotype control or anti-IL-10R abs per mouse one day before the adoptive transfer. (D) The percentage of CD4+CD25+FoxP3+ Treg cells was determined in the lungs of recipient mice. Each graph represents three independent experiments, consisting of five mice per group.
Mentions: In order to identify the dominant organ with IL-10-producing B cells during infection, we isolated B cells from organs that have previously been described to harbor regulatory B cells (spleen), drain schistosome infection sites (mesenteric lymph nodes, MLN) or are the effector site where allergic inflammation is found (lung). Both pulmonary and splenic B cells, but not mesenteric B cells, from chronically-infected mice were able to produce IL-10 upon soluble egg antigen (SEA) stimulation, with highest production by splenic B cells (Fig. 2A). To study the suppressive activity of isolated B cells from different organs in downmodulating AAI, we adoptively transferred CD19+ B cells from OVA-infected mice into OVA-sensitized recipient mice. AAI was reduced by pulmonary or splenic but not by mesenteric B cells (Fig. 2B). Interestingly, the protective effect of the transfer of splenic B cells, but not of pulmonary B cells, was abolished by administering a blocking IL-10 receptor antibody (Fig. 2C). Furthermore, we observed increased percentages of CD4+CD25+FoxP3+ T cells in the lungs of recipient mice, but only after administering splenic B cells (Fig. 2D). This data indicate that pulmonary B cells can drive IL-10 and Treg cell-independent protection against eosinophilic AAI, while splenic B cells protect via an IL-10-dependent mechanism and enhance local Treg cell numbers in the lungs.

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