Deficiency in TLR4 impairs regulatory B cells production induced by Schistosome soluble egg antigen

Regulatory B cells (Bregs) producing IL-10 have negative regulatory function. Several studies have shown the important roles for Toll-like receptor 2 (TLR2), TLR4, and TLR9 ligation in the development of Bregs. We have reported that Schistosome soluble egg antigen (SEA) induced the production of Bregs. However, it remains unclear whether such activation is via the TLR pathway. The present study showed that IL-10 and TLR4 mRNA expression in spleen B cells of significantly increased in C57BL/10 J mice spleen B cells following SEA stimulation. The level of secreted IL-10 and IL-10+ B cell proportion decreased in spleen B cells derived from TLR4-deficient C57BL/10ScNJ (TLR4-/-) mice following SEA or LPS stimulation compared with C57BL/10 J mice. The CD1dhiCD5+ B cells proportion decreased in spleen B cells of TLR4-/- mice following SEA stimulation compared with control mice. NF-κB, ERK, p38MAPK and JNK signal transduction inhibitors significantly suppressed IL-10 secretion in CD1dhiCD5+ B cells induced by SEA or LPS. The phosphorylation levels of IκBα, p65, ERK, JNK and p38 were increased in CD1dhiCD5+ B cell of C57BL/10 J mice treated with LPS or SEA. In conclusion, this study suggests that TLR4 plays a critical role in Bregs activation induced by SEA. And the TLR4-triggered NF-κB and MAPK pathways activation in CD1dhiCD5+ B cells stimulated with SEA. The findings elucidated the mechanism of SEA induction of CD1dhiCD5+ B cells and helped us to understand the immune regulation during Schistosoma japonicum infection.