Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion.
Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion.
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A 组链球菌 S 蛋白利用红细胞作为免疫伪装，是免疫逃避的关键决定因素。
DOI：
10.1016/j.celrep.2019.11.001
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发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Gonzalez,DavidJ
中科院分区：
文献类型：
--
作者：
Wierzbicki,IgorH;Campeau,Anaamika;Dehaini,Diana;Holay,Maya;Wei,Xiaoli;Greene,Trever;Ying,Man;Sands,JennaS;Lamsa,Anne;Zuniga,Elina;Pogliano,Kit;Fang,RonnieH;LaRock,ChristopherN;Zhang,Liangfang;Gonzalez,DavidJ
群astreplant（GAS）是一种人类特异性病原体，通过多种毒力因子的加工来逃避宿主的免疫应答。虽然许多这些因素已被研究，许多蛋白质编码的GAS基因组是未知的功能。在此，我们描述了一种仿生红细胞（RBC）捕获的蛋白质的未知功能，随后注释为S蛋白在GAS病理生理学。S蛋白保持GAS的疏水性，它的缺失会降低人血液中的存活率。S蛋白促进GAS与裂解红细胞的包被以促进分子模拟，这增加了体外和体内的亲和力。蛋白质组学分析表明，S蛋白从GAS中的去除改变了细胞和细胞外的蛋白质景观，并伴随着几个关键的GAS毒力determinators.In体内，S蛋白的缺失导致毒力显着减弱，并促进了强大的免疫应答和免疫记忆的丰度下降。
Group AStreptococcus(GAS) is a human-specific pathogen that evades the host immune response through the elaboration of multiple virulence factors. Although many of these factors have been studied, numerous proteins encoded by the GAS genome are of unknown function. Herein, we characterize a biomimetic red blood cell (RBC)-captured protein of unknown function—annotated subsequently as S protein—in GAS pathophysiology. S protein maintains the hydrophobic properties of GAS, and its absence reduces survival in human blood. S protein facilitates GAS coating with lysed RBCs to promote molecular mimicry, which increases virulencein vitroandin vivo. Proteomic profiling reveals that the removal of S protein from GAS alters cellular and extracellular protein landscapes and is accompanied by a decrease in the abundance of several key GAS virulence determinants.In vivo, the absence of S protein results in a striking attenuation of virulence and promotes a robust immune response and immunological memory.