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.

Zehan Hu ^# ¹ ², Chenlu Zhang ^# ³, Luis Sifuentes-Dominguez ⁴, Christina M Zarek ¹, Daniel C Propheter ¹, Zheng Kuang ¹, Yuhao Wang ¹, Mihir Pendse ¹, Kelly A Ruhn ¹, Brian Hassell ¹, Cassie L Behrendt ¹, Bo Zhang ¹, Prithvi Raj ¹, Tamia A Harris-Tryon ³, Tiffany A Reese ¹, Lora V Hooper ¹ ²

Affiliations

1 Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3 Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
4 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
# Contributed equally.

PMID: 34735226 DOI: 10.1126/science.abe6723

Abstract

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.

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