The excretory-secretory products of Echinococcus granulosus protoscoleces stimulated IL-10 production in B cells via TLR-2 signaling

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.Electronic supplementary materialThe online version of this article (10.1186/s12865-018-0267-7) contains supplementary material, which is available to authorized users.

Therapeutic Efficacy of Excretory-Secretory Products of Trichinella spiralis Adult Worms on Sepsis-Induced Acute Lung Injury in a Mouse Model

“…In this study, we confirmed septic ALI in a CLP-induced sepsis mouse model characterized by structure damage and inflammatory cell infiltration, pulmonary edema in lung tissue accompanied by the increased levels of pro-inflammatory cytokines, which closely mimicked the pathophysiological characteristics of acute lung injury observed in clinical patients. The ES products of helminth have been regarded as key molecules secreted by helminth in regulating host inflammation, cell apoptosis, protein degradation and antigen presentation (Crowe et al, 2017;Smallwood et al, 2017;Pan et al, 2018;Sun et al, 2019a). Previous studies have determined that Ts-AES enabled to induce strong Tregs responses, characterized by increased CD4 + CD25 + Foxp3 + and CD4 + CD25 − Foxp3 + Treg cells accompanied by high levels of IL-10 and TGF-b (Sun et al, 2019b).…”

Microarray Analysis of lncRNA and mRNA Reveals Enhanced Lipolysis Along With Metabolic Remodeling in Mice Infected With Larval Echinococcus granulosus

“…The protoscoleces of E. granulosus (EgPSC) were obtained from the hydatid cysts of naturally infected sheep livers under aseptic conditions, and washed three times using 0.9% NaCl containing 100 mg/ml penicillin and 100 U/ml streptomycin. Female C57BL/6J mice were intraperitoneally injected with a 200 μl suspension containing 2000 live EgPSC in 0.9% NaCl to establish the Eg model, and the control mice were received 200 μl 0.9% NaCl ( Pan et al, 2013 , 2018 ; Yu et al, 2018 ). The infected and control mice were sacrificed for experiment after 7 months of infection.…”

“…E. granulosus can infect many intermediate hosts and go unnoticed for several decades, since it has evolved strategies to subvert the immune responses ( Peón et al, 2016 ). Previous studies have focused on the immunoregulatory role of E. granulosus and its derived molecules ( Pan et al, 2013 , 2018 ; Díaz, 2017 ). However, their metabolic regulatory activity of E. granulosus and its derived molecules has been largely neglected.…”

Comprehensive Analysis of Non-coding RNA Profiles of Exosome-Like Vesicles From the Protoscoleces and Hydatid Cyst Fluid of Echinococcus granulosus

“…A proteomic analysis of the exosome-like vesicles (ELVs) from the HF of E. granulosus– infected fertile sheep identified a number of host proteins and parasite-derived proteins, among which antigen B and antigen five could reach the host and elicit a strong specific antibody response (Siles-Lucas et al, 2017 ). For E. granulosus PSCs, the excretory/secretory products can directly regulate the differentiation of B10, B17, and Th17 cells, and stimulated B10 cells produce interleukin (IL)10 via Toll-like receptor 2 (TLR2) signaling (Pan et al, 2017 , 2018 ). A recent study isolated and analyzed the proteome of PSC–ELVs, which can be internalized by dendritic cells and induce their maturation (Nicolao et al, 2019 ).…”