While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia. As a rich store of F-actin, pyroptotic filopodia are recognized by dendritic cells through the F-actin receptor, CLEC9A (DNGR1). We propose that cells assemble filopodia before cell rupture to serve as a posthumous mark for a cell that has died by gasdermin-induced pyroptosis, or MLKL-induced necroptosis, for recognition by dendritic cells. This study reveals the spectacular morphology of pyroptosis and identifies a mechanism by which inflammasomes induce pyroptotic cells to construct a de novo alarmin that activates dendritic cells via CLEC9A, which coordinates the transition from innate to adaptive immunity^1,2.

虽然细胞凋亡会破坏细胞以增强免疫沉默，但焦亡细胞死亡会引发炎症。对于经历焦亡的细胞的结构结构以及焦亡尸体是否具有免疫原性，我们知之甚少。在这里，我们报道了炎性小体在焦亡细胞破裂前几分钟从质膜触发丝状伪足的 Gasdermin-D 和钙依赖性爆发，从而用丝状伪足冠状尸体。作为 F-肌动蛋白的丰富储存库，焦亡丝状伪足可通过 F-肌动蛋白受体 CLEC9A （DNGR1） 被树突状细胞识别。我们建议细胞在细胞破裂前组装丝状伪足，作为因 gasdermin 诱导的焦亡或 MLKL 诱导的坏死性凋亡而死亡的细胞的死后标记，以供树突状细胞识别。这项研究揭示了焦亡的壮观形态，并确定了炎症小体诱导焦亡细胞构建从头警报蛋白的机制，该警报蛋白通过 CLEC9A 激活树突状细胞，CLEC9A 协调从先天免疫到适应性免疫的转变^1,2。