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

Science. 2021 Nov 5;374(6568):eabe6723. doi: 10.1126/science.abe6723. Epub 2021 Nov 5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load
  • Cell Membrane / metabolism
  • Cell Membrane Permeability
  • Cornified Envelope Proline-Rich Proteins / genetics
  • Cornified Envelope Proline-Rich Proteins / metabolism*
  • Cytokines / metabolism
  • Disease Susceptibility
  • Gastrointestinal Microbiome*
  • Goblet Cells / metabolism
  • Gram-Positive Bacteria / physiology*
  • Humans
  • Immunity, Innate
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Intestines / microbiology*
  • Listeria monocytogenes / physiology
  • Listeriosis / microbiology
  • Mice
  • Microbial Viability
  • Nematospiroides dubius*
  • Paneth Cells / metabolism
  • Pore Forming Cytotoxic Proteins / genetics
  • Pore Forming Cytotoxic Proteins / metabolism
  • Strongylida Infections / immunology*
  • Strongylida Infections / metabolism
  • Strongylida Infections / microbiology


  • Cornified Envelope Proline-Rich Proteins
  • Cytokines
  • Pore Forming Cytotoxic Proteins
  • SPRR2A protein, human
  • Sprr2a1 protein, mouse