Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science. 2021 Nov 5;374(6568):eabe6723. doi: 10.1126/science.abe6723.
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 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.
一组多样化的抗菌蛋白 (AMPs) 有助于保护哺乳动物的肠道免受各种微生物的挑战。我们发现，小脯氨酸丰富蛋白 2A (SPRR2A) 是一种肠道抗菌蛋白，与先前发现的哺乳动物 AMP 没有系统发育关系。在这项研究中，SPRR2A 在 Paneth 细胞和杯状细胞中表达，并通过破坏其膜选择性地杀死革兰氏阳性菌。SPRR2A 改变了肠道微生物群落的组成，限制了细菌与肠道表面的联系，并防止了感染。SPRR2A 与其他肠道 AMP 的不同之处在于，它是由寄生虫感染过程中产生的 2 型细胞因子诱导的。此外，SPRR2A 可防止寄生虫诱导的肠道组织细菌入侵。因此，SPRR2A 是一种由 2 型免疫触发的独特 AMP，可在寄生虫感染期间保护肠道屏障。
