Division of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA.
Division of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA.
Immunity. 2019 Oct 15;51(4):609-624. doi: 10.1016/j.immuni.2019.08.005. Epub 2019 Aug 28.
Inflammasomes are supramolecular organizing centers that operate to drive interleukin-1 (IL-1)-dependent inflammation. Depending on context, inflammatory caspases act upstream or downstream of inflammasome assembly, serving as the principal enzymes that control activities of these organelles. In this review, we discuss mechanisms of inflammasome assembly and signaling. We posit that upstream regulatory proteins, classically known as pattern-recognition receptors, operate to assess infectious and non-infectious threats to the host. Threat assessment is achieved through two general strategies: (1) direct binding of receptors to microbial or host-derived ligands or (2) indirect detection of changes in cellular homeostasis. Upon activation, these upstream regulatory factors seed the assembly of inflammasomes, leading to IL-1 family cytokine release from living (hyperactive) or dead (pyroptotic) cells. The molecular and physiological consequences of these distinct cell fate decisions are discussed.
炎症小体是一种超分子组装中心，可驱动白细胞介素-1（IL-1）依赖性炎症。根据具体情况，炎性半胱天冬酶在上游或炎症小体组装的下游起作用，作为控制这些细胞器活性的主要酶。在这篇综述中，我们讨论了炎症小体的组装和信号转导机制。我们假设上游调节蛋白，通常称为模式识别受体，用于评估宿主受到的感染和非感染威胁。威胁评估是通过两种一般策略实现的：（1）受体与微生物或宿主来源的配体直接结合，或（2）间接检测细胞内稳态的变化。在激活后，这些上游调节因子引发炎症小体的组装，导致活（过度活跃）或死（细胞焦亡）细胞释放白细胞介素-1 家族细胞因子。讨论了这些不同细胞命运决定的分子和生理后果。
