Reg4 protects against Salmonella infection-associated intestinal inflammation via adopting a calcium-dependent lectin-like domain.

Salmonella Typhimurium (S. Tm) is Gram-negative flagellated bacteria that can cause food-borne gastroenteritis and diarrhea in human. Developing efficacious methods against Salmonella infection is still challenged. Herein, we report that regenerating islet-derived family member 4 (Reg4) has potent bactericidal activity against S. Tm. For the S. Tm-infected mice, Reg4 significantly inhibits colonization of S. Tm in the intestine and subsequently ameliorates intestinal inflammation. In vitro experiments, the addition of Reg4 significantly suppresses the growth and proliferation of Salmonella. Moreover, both human and mice Reg4 proteins restrain the Salmonella to invade the intestinal epithelia. Mechanistically, Reg4 performs bactericidal action against Salmonella via a motif (HDPQK) homologous to a calcium-dependent (C-type) lectin-like domain. Reg4 can specifically bind to the flagella of Salmonella to restrain bacterial motility and suppress the host inflammatory response. In conclusion, our findings identify that Reg4 acts as a new antimicrobial protein against Salmonella, which suggests Reg4 may have a great significance for developing novel agents against Salmonella infection-associated intestinal inflammation.