Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection

A diverse group of antimicrobial proteins (AMPs) helps protect the mammalian intestine from varied microbial challenges. We show that small proline-rich protein 2A (SPRR2A) is an intestinal antibacterial protein that is phylogenetically unrelated to previously discovered mammalian AMPs. In this study, SPRR2A was expressed in Paneth cells and goblet cells and selectively killed Gram-positive bacteria by disrupting their membranes. SPRR2A shaped intestinal microbiota composition, restricted bacterial association with the intestinal surface, and protected against Listeria monocytogenes infection. SPRR2A differed from other intestinal AMPs in that it was induced by type 2 cytokines produced during helminth infection. Moreover, SPRR2A protected against helminth-induced bacterial invasion of intestinal tissue. Thus, SPRR2A is a distinctive AMP triggered by type 2 immunity that protects the intestinal barrier during helminth infection.

Automated summary

SPRR2A is an intestinal antibacterial protein that selectively kills Gram-positive bacteria by disrupting their membranes. It shapes the composition of intestinal microbiota, restricts bacterial association with the intestinal surface, and protects against Listeria monocytogenes infection. Additionally, SPRR2A is induced by type 2 cytokines during helminth infection and protects against bacterial invasion of intestinal tissue during this process.