Schistosomes Induce Regulatory Features in Human and Mouse CD1dhi 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 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.

IL-4 and IFN-γ induced by human immunodeficiency virus vaccine in a schistosome infection model

“…Van der Vlugt and colleagues pointed out that schistosomes have the capacity to drive the development of IL-10-producing regulatory CD1d hi B cells in both mice and humans. 35 Furthermore, these B cells are instrumental in reducing experimental allergic inflammation in mice. 35 Fairfax's data suggested that during chronic schistosomiasis, IL-10 promotes the development of a population of B cells within the liver that is responsible for minimizing inflammation and preventing the development of disease in the lungs.…”

“…35 Furthermore, these B cells are instrumental in reducing experimental allergic inflammation in mice. 35 Fairfax's data suggested that during chronic schistosomiasis, IL-10 promotes the development of a population of B cells within the liver that is responsible for minimizing inflammation and preventing the development of disease in the lungs. 36 On the other hand, IL-10 appears to block development of resistance to re-infection with S. mansoni.…”

Inmunorregulación inducida por helmintos: una actualización

“…En ratones, se describió que la capacidad supresora de la respuesta alérgica que tiene Schistosoma mansoni es dependiente de linfocitos B (LB) productores de IL-10 que se encuentran principalmente en la zona marginal del bazo. Estos inducen la conversión de un mayor número de células al fenotipo CD25+Foxp3 que los LB foliculares del mismo órgano (28). Recientemente, en un modelo de artritis, el desarrollo de esta enfermedad se asoció a un menor número de LB productores de IL-10, lo cual se revirtió al ser tratados con ES-62, un producto de excreción/secreción de Acantocheilonema vitae (32).…”

“…Hay dos estudios en humanos que han indagado la relación entre los Breg y la infección por Schistosoma haematobium. En gaboneses, se encontró un mayor porcentaje de Breg en los infectados que en los no infectados (28). En otra publicación (30), este mismo grupo investigó el papel funcional de estas cé-lulas en el humano y encontró que la depleción de la fracción de linfocitos B CD1d hi resultaba en un menor desarrollo de linfocitos T IL-10 + .…”

Bregs in Chronic HBV: Is It Time for Bragging Rights?

“…Breg producing IL-10 may limit schistosomiasis-related liver disease [8]. In human immunodeficiency virus (HIV)-1 infection, IL-10-producing B cells, which suppress HIV-1-specific T cell responses in vitro, are elevated in early and chronic HIV-1 infection [9].…”