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Abstract Background Therapeutic potential of helminth have been shown to have a protective effect on immune-mediated diseases such as Crohn's disease (CD), which is associated with increased production of T helper cell type 1. However, helminth therapy is unacceptable to patients due to side-effects and the fear of parasites. As helminths regulate the cellular immune responses through innate cells such as dendritic cells (DCs), cellular immunotherapy has been considered a therapeutic option to treat CD. Methods Bone marrow-dendritic cells were generated, enriched and treated with Trichinella spiralis muscle larval excretory/secretory products (Ts -MLES). DCs maturation was measured by flow cytometry and cytokine production of DCs were measured by ELISA. Colitis was generated by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) solution. For adoptive transfer, Ts -MLES treated-DCs injected intravenously 24 h prior to TNBS challenge. Disease activity index (DAI) including weight loss, diarrhea, and bloody stool were measured. Colon segments were stained with hematoxylin and eosin (H.E.) and periodic acid schiff (PAS) staining for histological damage scoring. The relative mRNA expression of cytokines in colon was analyzed by RT-PCR. Cytokine production in colon was measured by ELISA. Splenocytes were separated and cytokine profiles including Th1 (IFN-γ), Th2 (IL-4, IL-13), and Treg subsets (IL-10, TGF-β) were analyzed by flow cytometry. Results Ts -MLES regulated the maturation and cytokine production of DCs. Ts -MLES -DC ameliorated the severity of the TNBS-induced colitis. In the colon and the spleen, Ts -MLES-DC decreased IFN-γ (Th1) significantly and increased Th2 (IL-4, IL-13)- and Treg (IL-10, TGF-β)- related cytokines. Conclusions Ts -MLES-DC ameliorated the severity of the TNBS-induced colitis through decreasing IFN-γ. Ts -MLES-DC skewed the Th1-mediated response toward the Th2 type and regulatory T cell response. Highlights • T. spiralis MLES (Ts -MLES) regulated DCs phenotype. • Ts -MLES-DC ameliorated the severity of the TNBS-induced colitis • Ts -MLES-DC inhibited Th1 immune response while enhancing the Th2 and Treg immune response in TNBS-induced colitis in vivo. [ABSTRACT FROM AUTHOR]

• Nod-like receptor pyrin domain containing 3 (NLRP3) expression is elevated in CD4+ T cells at 7 and 14 dpi. • NLRP3 participates in the control of the Th2 immune response during Trichinella spiralis infection. • NLRP3 influences the Th2 cell-mediated host defenses against Trichinella spiralis. The inflammasome is a key line of immune defense against invading infectious pathogens. However, knowledge of the role of nod-like receptor pyrin domain containing 3 (NLRP3) in Trichinella spiralis infection which characteristically induces T-helper 2 (Th2) immune responses is sparse. In this study, we investigated the role of NLRP3 in the protection against T. spiralis infection through the Th2 immune response. We show that NLRP3 expression in CD4+ T cells was significantly increased at 7 days post-infection of T. spiralis. Compared to wild-type (WT) CD4+ T cells, the expression of IL-4 mRNA was reduced in NLRP3−/− CD4+ T cells, however, the expression of IFN-γ mRNA was comparable between the two groups. Consistently, ELISA and flow cytometry analysis showed that NLRP3−/− CD4+ T cells secreted lower levels of IL-4 than CD4+ T cells from WT mice, whilst the levels of IFN-γ secreted by NLRP3−/− CD4+ T cells were of similar levels to those secreted by WT CD4+ T cells. In addition, we observed a significant reduction of IL-4 and IL-13 by ELISA in NLRP3 −/− mice at 1, 2 and 4 weeks post-infection. Furthermore, we found that adult worm survival was substantially prolonged and muscle larvae burden was significantly increased in NLRP3 −/− mice. We further show that NLRP3 promotes the host defense against T. spiralis through its participation in the differentiation of Th2 cells. These findings provide novel insights into parasite expulsion and highlight the importance of NLRP3 in the host defense against T. spiralis. [ABSTRACT FROM AUTHOR]

• The recombinant serine protease from newborn larval stage (NBL-SP) of trichinella spirails was expressed, purified and the endotoxin in NBL-SP was removed;. • NBL-SP alleviated the severity of TNBS-induced colitis in mice;. • NBL-SP skewed the Th1 and Th17 response induced by TNBS towards the Th2 and treg response. Inflammatory bowel disease (IBD) is a complex immune-mediated disease of gastrointestinal tract that is mainly driven by Th1/Th17 immune response. "Helminth therapy" has emerged, and helminth-derived immunoregulatory molecules are being used as safe and new therapeutic antigens for IBD. Recombinant serine protease (SP) from newborn Trichinella spiralis (T. spiralis) larvae (NBL) was expressed and purified. BALB/c mice were immunized with NBL-SP at 100 µg three times at an interval of 5 days. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration. The disease activity index (DAI) and macroscopic and microscopic scores of the colon were assessed to identify the effect of NBL-SP on experimental colitis. Cytokine production in the serum was analysed by meso scale discovery (MSD). Cytokine production in the colon was detected by ELISA. CD4+ T cell differentiation was measured by flow cytometry. NBL-SP alleviated TNBS-induced colitis in mice. The DAI, macroscopic and microscopic scores and colon length all showed a positive intervention effect of NBL-SP on experimental colitis. NBL-SP can weaken the increase in IFN-γ, TNF-α and IL-17 production as well as CD4+ IFN-γ+ T cell and CD4+IL-17+ T cell populations induced by colitis. Furthermore, the levels of Th2-related cytokines (IL-4, IL-5) and regulatory cytokines (IL-10, TGF-β) were elevated meanwhile the ratio of regulatory T cells (Tregs) and CD4+ IL-4 + T cells were increased by NBL-SP. NBL-SP of T. spiralis had a potential protective effect against IBD. NBL-SP skewed the Th1 and Th17-mediated response towards the Th2 and Treg response. [ABSTRACT FROM AUTHOR]