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 CD1dhi 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 CD1dhi 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 CD1dhi B cells and furthermore, these are instrumental in reducing experimental allergic inflammation in mice.
Highlights
The prevalence and severity of allergic diseases and asthma has increased over the last five decades in industrialized countries [1]
To determine whether B cells are a dominant source of IL-10 and whether this IL-10 is essential for protection against airway inflammation (AAI) during chronic schistosome infections, IL10-deficient B cell and control wild-type (WT) chimeric mice were generated and chronically infected with S. mansoni followed by an allergic OVA sensitization and challenge
IL-5, IL-13 and/or IL-10 were elevated in the bronchoalveolar lavage (BAL) fluid and mediastinal lymph nodes (MedLN) of OVA-infected IL-102/2 B cell mice compared to OVA-uninfected IL-102/2 B cell group, whereas these Th2 cytokines were reduced in OVA-infected WT mice (Fig. 1B, C)
Summary
The prevalence and severity of allergic diseases and asthma has increased over the last five decades in industrialized countries [1]. Many epidemiological studies have reported an inverse association between helminth infections, which are highly prevalent in developing countries, and allergic or auto-immune disorders [2,3,4]. In order to study the interaction between helminth infections and protection against allergic diseases, murine models of allergic airway inflammation (AAI) and helminth infection have been developed. H. polygyrus or T. spiralis infections protected against house dust mite-induced and/or ovalbumin (OVA)-specific AAI [5,6]. S. mansoni infection protected mice against OVA-induced airway hyperresponsiveness (AHR)[7]; protection was optimal during the chronic stage of infection, but not the acute stage [8]
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