Abstract
BackgroundExcretory-secretory products released by Echinococcus granulosus protoscoleces (EgPSC-ESPs) are well-known to regulate T cell responses. However, their direct influence on the differentiation of B cell subsets remains largely elusive. This study investigated the effects of EgPSC-ESPs on the differentiation of IL-10-producing B cells (B10), and explored the possible role of Toll-like receptor 2 (TLR-2) signaling in this process.ResultsIn comparison to phosphate buffered saline (PBS), B cells exposed to the excretory–secretory products (ESPs) generated higher percentages of B10 cells, with higher expression of IL-10 mRNA, and larger amount of IL-10 production, which were in a dose dependent way. The mRNA and protein expression of TLR-2 in the ESPs-stimulated B cells were significantly higher than those in PBS, which was consistent to the results in B cells isolated from EgPSC infected mice. Moreover, TLR-2−/− B cells in response to ESPs stimulation expressed lower levels of IL-10 mRNA and produced undetectable IL-10 in comparison to those in normal B cells. In addition, Phosphatase and tensin homolog deleted on chromosome ten/AKT/Phosphatidylinositol-3 kinase (PTEN/AKT/PI3K) pathway was activated in ESPs-treated B cells, which was also dependent on TLR-2 signaling. Pam3CSK4, the agonist of TLR-2, could mock the effects of ESPs on the expression of PTEN, AKT and PI3K.ConclusionOverall, this study revealed that TLR-2 signaling was required for B10 induction mediated by EgPSC-ESPs, which might be an immunomodulatory target against the parasite infection.
Highlights
Excretory-secretory products released by Echinococcus granulosus protoscoleces (EgPSC-excretory–secretory products (ESPs)) are wellknown to regulate T cell responses
LPS stimulated higher frequencies of IL-10-producing B cells (B10), expression of IL-10 mRNA and IL-10 production in comparison to those in phosphate buffered saline (PBS) and ESPs groups. These results showed EgPSC-ESPs could directly induce the differentiation of B10 cells in vitro
In conclusion, this study showed that EgPSC-ESPs directly triggered B cells to secrete IL-10 in vitro, which required Toll like receptor (TLR)-2 signaling while PTEN/AKT/Phosphatidylinositol-3 kinase (PI3K) pathway was activated
Summary
Excretory-secretory products released by Echinococcus granulosus protoscoleces (EgPSC-ESPs) are wellknown to regulate T cell responses. Their direct influence on the differentiation of B cell subsets remains largely elusive. B cells have been well established to negatively regulate immune responses in recent years, which were defined as regulatory B cells (Breg or B10 cells) [5] They evoked a variety of IL-10-dependent regulatory effects, including downregulation of proinflammatory cytokines, induction of Treg cells and production of TGF-β [6,7,8]. Stimulation with ESPs of Leishmania led to IL-10 production by splenic B cells [15] These studies implied that B10 cells were associated with parasite infection.
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