The septin cytoskeleton is primarily known for roles in cell division and host defense against bacterial infection. Despite recent insights, the full breadth of roles for septins in host defense is poorly understood. In macrophages, Shigella induces pyroptosis, a pro-inflammatory form of cell death dependent upon gasdermin D (GSDMD) pores at the plasma membrane and cell surface protein ninjurin-1 (NINJ1) for membrane rupture. Here, we discover that septins promote macrophage pyroptosis induced by lipopolysaccharide (LPS)/nigericin and Shigella infection, but do not affect cytokine expression or release. We observe that septin filaments assemble at the plasma membrane, and cleavage of GSDMD is impaired in septin-depleted cells. We found that septins regulate mitochondrial dynamics and the expression of NINJ1. Using a Shigella-zebrafish infection model, we show that septin-mediated pyroptosis is an in vivo mechanism of infection control. The discovery of septins as a mediator of pyroptosis may inspire innovative anti-bacterial and anti-inflammatory treatments.

septin 细胞骨架主要因在细胞分裂和宿主防御细菌感染方面的作用而闻名。尽管最近有了一些见解，但人们对脓蛋白在宿主防御中的作用的全面了解知之甚少。在巨噬细胞中，志贺氏菌会诱导焦亡，这是一种促炎性细胞死亡形式，依赖于质膜上的 Gasdermin D (GSDMD) 孔和导致膜破裂的细胞表面蛋白 ninjurin-1 (NINJ1)。在这里，我们发现脓毒症促进脂多糖（LPS）/尼日利亚菌素和志贺氏菌感染诱导的巨噬细胞焦亡，但不影响细胞因子的表达或释放。我们观察到隔膜丝在质膜上组装，并且在隔膜耗尽的细胞中 GSDMD 的裂解受到损害。我们发现脓毒蛋白调节线粒体动力学和 NINJ1 的表达。使用志贺氏菌-斑马鱼感染模型，我们表明脓毒症介导的细胞焦亡是一种体内感染控制机制。脓毒症作为焦亡介质的发现可能会激发创新的抗菌和抗炎治疗。