胡泽汗等Science突破:一种新型肠道抗菌蛋白,在寄生虫感染时保护肠屏障
  • SPRR2A是一种新型肠道抗菌蛋白,可在肠道菌群诱导下,经TLR-Myd88通路由潘氏细胞和杯状细胞表达分泌;
  • SPRR2A通过破坏细菌膜,选择性杀死革兰氏阳性细菌;
  • 分析其敲除小鼠表明,SPRR2A能塑造小肠菌群、限制革兰氏阳性菌在小肠黏液层定植和接触肠上皮,保护小鼠抵抗革兰氏阳性肠道致病菌的感染;
  • 肠道蠕虫感染期间,2型细胞因子IL-4和IL-13通过STAT6诱导SPRR2A高表达,从而抵抗因蠕虫感染破坏肠屏障引起的细菌对肠组织的入侵。
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mildbreeze
抗微生物蛋白(AMP)是宿主分泌的对粘膜表面病原体的一道重要防线。美国德克萨斯大学西南医学中心的Lora V. Hooper实验室胡泽汗和张晨璐等在Science发表的一项最新研究中,鉴定出一种新型杀菌蛋白SPRR2A(富含脯氨酸的小蛋白2A),在系统发育和作用机制上不同于已知的菌群诱导的AMP。该蛋白能选择性抑制革兰氏阳性的共生菌和致病菌,并能由抗寄生虫的2型免疫诱导,在肠道蠕虫感染期间保护肠屏障抵抗细菌入侵。
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Science [IF:47.728]

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

富含脯氨酸的小蛋白2A是一种在蠕虫感染期间调动的肠道杀菌蛋白

10.1126/science.abe6723

2021-11-05, Article

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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.

First Authors:
Zehan Hu,Chenlu Zhang

Correspondence Authors:
Zehan Hu,Tiffany A Reese,Lora V Hooper

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

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Cell Host and Microbe期刊

Helminths are positively AMPing up gut de-bugging

2022-01-12

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