The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different inflammasomes containing distinct sensor molecules exist. The NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that NLRP3 is recruited to mitochondria-associated endoplasmic reticulum membranes (MAMs) and is activated by MAM-derived effectors. Here, we show that in response to inflammasome activators, MAMs localize adjacent to Golgi membranes. Diacylglycerol (DAG) at the Golgi rapidly increases, recruiting protein kinase D (PKD), a key effector of DAG. Upon PKD inactivation, self-oligomerized NLRP3 is retained at MAMs adjacent to Golgi, blocking assembly of the active inflammasome. Importantly, phosphorylation of NLRP3 by PKD at the Golgi is sufficient to release NLRP3 from MAMs, resulting in assembly of the active inflammasome. Moreover, PKD inhibition prevents inflammasome autoactivation in peripheral blood mononuclear cells from patients carrying NLRP3 mutations. Hence, Golgi-mediated PKD signaling is required and sufficient for NLRP3 inflammasome activation.

炎症小体是感知组织损伤和感染因子以启动先天免疫反应的多蛋白复合物。存在含有不同传感器分子的不同炎症小体。NLRP3 炎症小体是独一无二的，因为它可以检测到各种危险信号。据报道，NLRP3 被募集到线粒体相关内质网膜 (MAM) 并被 MAM 衍生的效应子激活。在这里，我们表明，作为对炎症小体激活剂的反应，MAM 定位在高尔基体膜附近。高尔基体的二酰基甘油 (DAG) 迅速增加，募集 DAG 的关键效应蛋白激酶 D (PKD)。在 PKD 失活后，自寡聚化的 NLRP3 保留在与高尔基体相邻的 MAM 处，从而阻断活性炎性体的组装。重要的，PKD 在高尔基体对 NLRP3 的磷酸化足以从 MAM 中释放 NLRP3，从而导致活性炎性体的组装。此外，PKD 抑制可防止携带 NLRP3 突变的患者外周血单个核细胞中的炎性体自激活。因此，高尔基体介导的 PKD 信号传导是 NLRP3 炎性体激活所必需且足够的。