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Shiga toxin suppresses noncanonical inflammasome responses to cytosolic LPS
Science Immunology ( IF 17.6 ) Pub Date : 2020-11-27 , DOI: 10.1126/sciimmunol.abc0217
Morena S Havira 1 , Atri Ta 1 , Puja Kumari 1 , Chengliang Wang 1 , Ashley J Russo 1 , Jianbin Ruan 1 , Vijay A Rathinam 1 , Sivapriya Kailasan Vanaja 1
Affiliation  

Inflammatory caspase–dependent cytosolic lipopolysaccharide (LPS) sensing is a critical arm of host defense against bacteria. How pathogens overcome this pathway to establish infections is largely unknown. Enterohemorrhagic Escherichia coli (EHEC) is a clinically important human pathogen causing hemorrhagic colitis and hemolytic uremic syndrome. We found that a bacteriophage-encoded virulence factor of EHEC, Shiga toxin (Stx), suppresses caspase-11–mediated activation of the cytosolic LPS sensing pathway. Stx was essential and sufficient to inhibit pyroptosis and interleukin-1 (IL-1) responses elicited specifically by cytosolic LPS. The catalytic activity of Stx was necessary for suppression of inflammasome responses. Stx impairment of inflammasome responses to cytosolic LPS occurs at the level of gasdermin D activation. Stx also suppresses inflammasome responses in vivo after LPS challenge and bacterial infection. Overall, this study assigns a previously undescribed inflammasome-subversive function to a well-known bacterial toxin, Stx, and reveals a new phage protein-based pathogen blockade of cytosolic immune surveillance.



中文翻译:

志贺毒素抑制非典型炎症小体对细胞溶质 LPS 的反应

炎性半胱天冬酶 - 依赖的细胞溶质脂多糖 (LPS) 传感是宿主防御细菌的关键武器。病原体如何克服这一途径以建立感染在很大程度上是未知的。肠出血性大肠杆菌(EHEC) 是临床上重要的人类病原体,可引起出血性结肠炎和溶血性尿毒症综合征。我们发现 EHEC 的噬菌体编码毒力因子志贺毒素 (Stx) 抑制 caspase-11 介导的细胞溶质 LPS 传感途径的激活。Stx 对抑制细胞质 LPS 特异性引起的细胞焦亡和白细胞介素 1 (IL-1) 反应至关重要且足以抑制。Stx 的催化活性是抑制炎性体反应所必需的。炎症小体对胞质 LPS 反应的 Stx 损伤发生在 gasdermin D 激活水平。Stx 还在 LPS 攻击和细菌感染后抑制体内炎症小体反应。总体而言,这项研究将以前未描述的炎症小体破坏功能分配给了一种众所周知的细菌毒素 Stx,

更新日期:2020-11-27
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