Effects of Trichinella spiralis and its serine protease inhibitors on intestinal mucosal barrier function

T. spiralis is a highly pathogenic zoonotic nematode that poses significant public health risks and causes substantial economic losses. Understanding its invasion mechanisms is crucial. This study explored the role of serine protease inhibitors (SPIs) secreted by T. spiralis in disrupting the host intestinal epithelial barrier. The effects of T. spiralis infection on the jejunal barrier function in mice were investigated. Histopathological analysis showed significant jejunal damage, peaking at day 7 post-infection (dpi). RT-qPCR and Western blotting revealed marked reductions in tight junction proteins (ZO-1, Occludin, Claudin-3), mucins (MUC-1, MUC-2), and anti-inflammatory cytokines (TGF-β, IL-10) from 1 to 15 dpi, along with increased expression of Toll-like receptors (TLR-1, TLR-2, TLR-4) and pro-inflammatory cytokines (TNF-α, IL-1β). Recombinant SPIs (rKaSPI, rAdSPI) were purified and co-cultured with intestinal epithelial cells (IPECs) and used in mouse models. The protein expression changes in IPECs and mice were consistent with those in T. spiralis -infected tissues. Both SPIs downregulated ZO-1, Occludin, Claudin-3, MUC-1, MUC-2, TGF-β, and IL-10, while upregulating TLR-4 and pro-inflammatory cytokines, disrupting the intestinal barrier and exacerbating inflammation. Notably, rAdSPI had a more pronounced effect. In summary, T. spiralis infection caused significant jejunal damage and disrupted the intestinal barrier. T. spiralis -secreted SPIs, especially AdSPI, played a pivotal role, facilitating invasion by compromising the host’s intestinal barrier and promoting inflammation. This study provides insights into T. spiralis invasion mechanisms and potential targets for trichinellosis prevention and control.