Background A Trichinella spiralis serine proteinase (TsSPc) was identified in the intestinal infective larva (IIL) surface and excretory-secretory (ES) antigens. Our previous study showed that recombinant TsSPc (rTsSPc) disrupted intestinal epithelial integrity and barrier function, and mediated larval invasion of intestinal mucosa. This study aims to investigate the impact of rTsSPc vaccination on intestinal epithelial integrity and its elicited protective immunity in a mouse model. Methodology/principal finding ELISA results demonstrated that rTsSPc immunization induced a systemic humoral immune response with serum-specific IgG antibody titer reaching 1:10⁵, and elicited a mixed Th1/Th2 immune response dominated by the Th2 type. In the rTsSPc immunized mice, the TsSPc-specific intestinal sIgA level was also markedly increased ( P < 0.0001); The secretion levels of IFN-γ and IL-4 in spleen, mesenteric lymph node (MLN) and Peyer’s patch (PP) cells were significantly increased ( P < 0.0001). rTsSPc immunization blocked the binding of parasite-derived TsSPc and gut epithelial RACK 1 receptor, prevented the activation of MAPK/ERK1/2 pathway and enhanced gut epithelial integrity, and impeded the parasite invasion. Vaccination of mice with rTsSPc exhibited a 65.7% reduction of enteral adult burden with a 61.13% decline of female fecundity, and a 58.10% reduction of muscle larval burden. Intestinal inflammation of rTsSPc-immunized mice was also significantly alleviated, as demonstrated that goblet cell numbers were obviously decreased, expression level of mucins (Muc2 and Muc5ac), pro-inflammatory cytokines (IL-6 and TNF-α) was evidently declined, while expression level of anti-inflammatory cytokines (IL-10 and TGF-β) was distinctly increased after infection. Moreover, peritoneal macrophages of rTsSPc-immunized mice exhibited a mixed M1/M2 polarization, but shifted to a predominant M2 polarization pattern post infection. ADCC assay confirmed that peritoneal macrophage of immunized mice had a stronger anti-rTsSPc antibodies-mediated cytotoxicity killing newborn larvae ( P < 0.0001). Conclusions rTsSPc vaccination produced a high protective immunity through multiple synergistic mechanisms: eliciting an obvious humoral and cellular immunity, gut local mucosal sIgA responses; blocking the binding of parasite-derived TsSPc to gut RACK1 receptors and the activation of MAPK/ERK1/2 pathway, improved gut epithelial integrity, inhibiting larval invasion, enhancing macrophages’ ability of ADCC killing larvae, and finally reduced parasite burden and alleviated inflammation of intestines and skeletal muscles. TsSPc might be a promising novel candidate target for anti- T. spiralis vaccine.
Wu et al. (Tue,) studied this question.