A Trichinella spiralis serine protease mediates larva invasion of gut mucosa via inducing enterocyte apoptosis and damaging barrier integrity in mice.

We aimed to determine if T. spiralis serine protease (TsSPc) facilitates larval invasion through triggering apoptosis in gut epithelial cells and impairing the barrier function in mice. The findings revealed that rTsSPc binds to and interacts with PGAM5 receptor in enterocyte, thereby activating the apoptosis pathway and causing enterocyte apoptosis. Additionally, rTsSPc decreased tight junctions (TJs) protein expression, compromised intestinal epithelium integrity, elevated intestinal permeability, and ultimately promoted larvae invading to intestinal mucosa. When a phosphoglycerate mutase family member 5 (PGAM5) receptor inhibitor (LFHP-1c) and apoptosis inhibitor (Z-VAD-FMK) were administrated in mice, and the TJs expression in murine gut was obviously increased and intestinal permeability was evidently decreased. Additionally, when mice were administrated with the two inhibitors and followed by challenge with T. spiralis muscle larvae, intestinal adult worm burdens were significantly decreased. Moreover, two inhibitors also reduced pro-inflammatory cytokines (IL-1β and TNF-α) expression and increased anti-inflammatory cytokines (IL-10 and IL-4) expression, thereby alleviated intestinal mucosal inflammation and injury. These findings indicated that TsSPc interacting with PGAM5 induced gut epithelial apoptosis, damaged gut epithelial barrier function, thereby facilitating larva invasion of gut mucosa. TsSPc is an invasive virulence factor and might be a potential candidate for vaccine development to block T. spiralis infection.