Abstract：
Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1β (IL-1β), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1α), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1β production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1β production, indicating that IRE1α is required for CT- or CTB-induced IL-1β production in RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages.
摘要：
霍乱毒素(CT),由一个A亚基（CTA）和五个B亚基（CTB）组成的细菌外毒素，作为免疫佐剂。CTB可以诱导白细胞介素-1β（IL-1β）的产生，一种促炎细胞因子，与脂多糖（LPS）协同作用，从驻留的腹膜巨噬细胞（RPM）通过pyrin和NLRP3炎性体。然而,CTB或CT如何激活巨噬细胞中的这些炎性体还不清楚.这里,我们阐明了需要肌醇的酶1α（IRE1α）的作用，内质网（ER）应力传感器，在CT诱导的RPM中产生IL-1β。在RPM中，CTB掺入ER并诱导ER应激反应，取决于GM1，一种细胞膜神经节苷脂。IRE1α缺陷的RPM显示对CT或CTB诱导的IL-1β产生的显着损害，表明IRE1α是CT或CTB诱导的IL-1β产生所必需的。这项研究证明了IRE1α在组织驻留巨噬细胞中激活NLRP3和pyrin炎性体中的关键作用。
