The immune system has evolved multiple mechanisms to restrict microbial infections and regulate inflammatory responses. Without appropriate regulation, infection-induced inflammatory pathology can be deadly. The innate immune system recognizes the microbial molecules conserved in many pathogens and engages a rapid response by producing inflammatory mediators and activating programmed cell death pathways, including pyroptosis, apoptosis, and necroptosis. Activation of pattern recognition receptors, in combination with inflammatory cytokine-induced signaling through death domain-containing receptors, initiates a highly interconnected cell death process called PANoptosis (pyroptosis, apoptosis, necroptosis). Broadly speaking, PANoptosis is critical for restricting a wide range of pathogens (including bacteria, viruses, fungi, and parasites), which we describe in this review. We propose that re-examining the role of cell death and inflammatory cytokines through the lens of PANoptosis will advance our understanding of host–pathogen evolution and may reveal new treatment strategies for controlling a wide range of infectious diseases.

免疫系统已经进化出多种机制来限制微生物感染和调节炎症反应。如果没有适当的监管，感染引起的炎症病理学可能是致命的。先天免疫系统识别许多病原体中保守的微生物分子，并通过产生炎症介质和激活程序性细胞死亡途径（包括细胞焦亡、细胞凋亡和坏死性凋亡）进行快速反应。模式识别受体的激活，结合炎性细胞因子通过包含死亡结构域的受体发出的信号，启动了一个高度相互关联的细胞死亡过程，称为 PANoptosis（细胞凋亡，一种细胞凋亡，n坏死）。从广义上讲，PANoptosis 对于限制我们在本综述中描述的多种病原体（包括细菌、病毒、真菌和寄生虫）至关重要。我们建议，通过 PANoptosis 的镜头重新审视细胞死亡和炎性细胞因子的作用，将促进我们对宿主-病原体进化的理解，并可能揭示控制多种传染病的新治疗策略。