Inflammasome activation by Salmonella typhimurium biofilms

摘要 Nod样受体(NLRs)胞浆激活诱导组装 炎性小体是激活炎性半胱氨酸酶的胞浆多蛋白复合体 (caspase-1和-11)。这些半胱氨酸天冬氨酸酶促进前IL-1和前IL-18的切割激活 IL-1和IL-18，还会引发下垂，这是一种炎性细胞死亡，杀死受感染的细胞。 IL-1是一种关键的细胞因子，参与了多种炎症性疾病的发病机制 疾病以及细菌感染，包括肠道沙门氏菌、鼠伤寒沙门氏菌(S. 鼠伤寒杆菌)感染。NLRP3是最具特征性的炎症体，可以被激活 具有广泛的危险信号，并使用与凋亡相关的斑点样蛋白，包含 作为接头分子的卡片(ASC)。尽管如此，触发NLRP3组装的分子 在此期间，鼠伤寒沙门氏菌的感染情况尚不清楚。 由细菌和人类产生的淀粉样蛋白的特征是它们的 保守的交叉-Sheet四元结构。淀粉样纤维是一种重要的细胞外基质 由不同的细菌群形成的生物膜的组成部分。有趣的是，人类淀粉样蛋白-，胰岛 淀粉样多肽和血清淀粉样蛋白A(SAA)都被证明可以激活 NLRP3炎症小体导致IL-1的产生。 我们的长期目标是阐明细菌淀粉样蛋白在微生物宿主中的作用。 互动。在鼠伤寒沙门氏菌的生物膜中产生的淀粉样纤维被称为卷曲和 已被证明在感染期间表达。此应用程序的目标是确定 细菌淀粉样卷曲是否会通过激活NLRP3触发IL-1和IL-18的产生 在鼠伤寒沙门氏菌感染期间。

Summary Activation of cytosolic activation of Nod like receptors (NLRs) induces the assembly of inflammasomes, which are cytosolic multiprotein complexes that activate inflammatory caspases (caspase-1 and -11). These caspases promote the cleavage of pro-IL-1 and pro- IL-18 to active IL-1 and IL-18, triggering also pyroptosis, an inflammatory cell death that kills the infected cell. IL-1 is a key cytokine that has been implicated in the pathogenesis of several inflammatory diseases as well as bacterial infections including Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. NLRP3 is the best-characterized inflammasome, which can be activated with a wide range of danger signals and uses apoptosis-associated speck-like protein containing a CARD (ASC) as an adaptor molecule. Nonetheless, the molecule that trigger NLRP3 assembly during S. Typhimurium infection is not known. Amyloid proteins, produced both by bacteria and humans, are characterized by their conserved cross--sheet quaternary structure. Amyloid fibers are an important extracellular matrix component of biofilms formed by diverse groups of bacteria. Intriguingly, human amyloid-, islet amyloid polypeptide and serum amyloid A (SAA) have all been demonstrated to activate the NLRP3 inflammasome resulting in the production of IL-1 . Our long-range goal is to elucidate the role of bacterial amyloids in microbe-host interactions. Amyloid fibers produced in the biofilms of S. Typhimurium are termed curli and have been shown to be expressed during infection. The objective of this application is to determine whether bacterial amyloid curli would trigger IL-1 and IL-18 production through NLRP3 activation during S. Typhimurium infection.