Abstract

The specific regulatory mechanism of bladder urothelial barrier dysfunction after infection with Uropathogenic E. coli (UPEC) is still unclear. The crosstalk between bladder urothelial cells and mast cells may play an important role during UPEC infection. In this study, the pyroptosis of urothelial cells was investigated after UPEC infection both in vivo and in vitro. The levels of IL-1β and IL-18 in the exosomes derived from bladder urothelial cell after UPEC infection was detected. The role of these processes in the recruitment and activation of mast cells was measured. The mechanism of mast cell-induced disruption of bladder epithelial barrier function was also assessed. We found that UPEC infection induced pyroptosis of bladder urothelial cells and led to the release of IL-1β and IL-18 in the form of exosomes, which promoted the migration of mast cells. Tryptase secreted by the mast cells aggravated the damage to the barrier function of bladder urothelium by acting on protease-activated receptor 2 (PAR2). Inhibition of pyroptosis or tryptase-PAR2 axis reduced the disruption of bladder urothelial barrier function and decreased the bacterial burden. The present study supported a novel mechanism by which pyroptosis-dependent release of exosomes from bladder urothelial cells activated the mast cells and regulated bladder urothelial barrier function during UPEC infection.