Trichinellosis is a serious zoonotic parasitic disease caused by Trichinella spiralis (T. spiralis) that causes considerable economic losses for the global pig breeding and food industries. As such, there is an urgent need for a vaccine that can prevent T. spiralis infection. Previous studies have reported that recombinant invasive Lactococcus lactis (LL) expressing Staphylococcus aureus fibronectin binding protein A (LL-FnBPA+) can transfer DNA vaccines directly to dendritic cells (DCs) across an epithelial cell monolayer, leading to significantly higher amounts of heterologous protein expression compared to non-invasive Lactococcus lactis. In this study, the invasive bacterium Lactiplantibacillus plantarum (L. plantarum) expressing FnBPA was used as a carrier to deliver a novel oral DNA vaccine consisting of T. spiralis adult putative serine protease (Ts-ADpsp) and murine interleukin (IL)-4 DNA to mouse intestinal epithelial cells. Experimental mice were orally immunized 3 times at 10-day intervals. At 10 days after the last vaccination, mice were challenged with 350 T. spiralis infective larvae by oral inoculation. Immunization with invasive L. plantarum harboring pValac-Ts-ADpsp/pSIP409-FnBPA induced the production of anti-Ts-ADpsp-specific IgG of serum, type 1 and 2 helper T cell cytokines of mesenteric lymph node (MLN) and spleen, secreted (s) IgA of intestinal lavage, and decreased T. spiralis burden and intestinal damage compared to immunization with non-invasive L. plantarum expressing Ts-ADpsp (pValac-Ts-ADpsp/pSIP409). Thus, invasive L. plantarum expressing FnBPA and IL-4 stimulates both mucosal and cellular immune response to protect against T. spiralis infection, highlighting its therapeutic potential as an effective DNA vaccine for trichinellosis.
Trichinellosis is an important foodborne zoonosis, and no effective treatments are yet available. Nod-like receptor (NLR) plays a critical role in the host response against nematodes.
Background: Trichinellosis is an important food-borne zoonosis, and no effective treatments are yet available. Nod-like receptor plays a critical role in the host response against nematodes. Therefore, we aimed to explore the role of the NLRP3 inflammasome (NLRP3) during the adult, migrating, and encysted stages of Trichinella spiralis (T. spiralis) infection. Methods: The mice were treated with the specific NLRP3 inhibitor MCC950 after inoculation with T. spiralis. Then, NLRP3 plays the role in T. spiralis-infected mice were evaluated using ELISA, Western blotting, Flow cytometry, Histopathological evaluation, Bone marrow-derived macrophage (BMDM) stimulation and immunofluorescenceResults: The in vivo results showed that NLRP3 enhanced the Th1 immune response in the adult stage and the migrating stage and weakened the Th2 immune response in the encysted stage. NLRP3 promoted the release of proinflammatory factors (INF-γ) and suppressed the release of anti-inflammatory factors (IL-4). Pathological changes were also improved in the absence of NLRP3 in mice during T. spiralis infection. Importantly, a significant reduction in adult worm burden and muscle larvae burden at 7 and 35 days post infection was observed in mice treated with the specific NLRP3 inhibitor MCC950. In vitro, we first demonstrated that NLRP3 in macrophages can be activated by T. spiralis proteins and promotes IL-1β and IL-18 release. Conclusions: This study revealed that the NLRP3 is involved in the host response to T. spiralis infection and that targeted inhibition of NLRP3 enhanced the Th2 response and accelerated T. spiralis expulsion. These findings may help in the development of protocols for controlling trichinellosis.
Trichinellosis caused by Trichinella spiralis (T. spiralis) is a zoonotic disease that seriously endangers human health. At present, vaccines that used to prevent trichinellosis was an effective way, but the production of antibody levels and immunogenicity is weakness. Adjuvants has been studied to elevate the antibody levels and immunogenicity of the vaccines. Therefore, it is urgent need to develop an effective adjuvant for the T. spiralis vaccine. The recent studies have indicated that traditional Chinese medicine polysaccharides as adjuvants can play a promote role in vaccine and it is a low-toxicity, and biodegradable compound. In this study, BALB/c mice were orally inoculated with recombinant Lactobacillus plantarum (L. plantarum) vaccine expressing T. spiralis cathepsin F-like protease 1 gene (rTs-CPF1), and it was administered thrice in the same dose at 10 days intervals. Meanwhile, Lycium barbarum polysaccharide (LBP) was orally administration until to 37 days. Mice were infected with 350 T. spiralis muscle larvae (ML) at 37 days after the first immunization. The results showed that LBP enhanced specific IgG and sIgA antibody levels against T. spiralis CPF1 protein in mice immunized with L. plantarum rTs-CPF1 + LBP group compared with L. plantarum rTs-CPF1 group. Moreover, LBP improved the expression levels of IFN-γ and IL-4, and the numbers of intestinal and intramuscular worm burden was significantly decreased in L. plantarum rTs-CPF1 + LBP group compared to L. plantarum rTs-CPF1 group. The reduction rate of adult worm and ML burden reached 47.31% and 68.88% in L. plantarum rTs-CPF1 + LBP group, respectively. In conclusion, LBP have a promoting role on the immunoprotective effects of T. spiralis vaccine and it may be considered as a novel adjuvant against parasitic vaccine.
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