Division of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
Nat Cell Biol. 2024 Sep;26(9):1420-1433. doi: 10.1038/s41556-024-01491-y. Epub 2024 Sep 2.
Innate immunity, cell death and inflammation underpin many aspects of health and disease. Upon sensing pathogens, pathogen-associated molecular patterns or damage-associated molecular patterns, the innate immune system activates lytic, inflammatory cell death, such as pyroptosis and PANoptosis. These genetically defined, regulated cell death pathways not only contribute to the host defence against infectious disease, but also promote pathological manifestations leading to cancer and inflammatory diseases. Our understanding of the underlying mechanisms has grown rapidly in recent years. However, how dying cells, cell corpses and their liberated cytokines, chemokines and inflammatory signalling molecules are further sensed by innate immune cells, and their contribution to further amplify inflammation, trigger antigen presentation and activate adaptive immunity, is less clear. Here, we discuss how pattern-recognition and PANoptosome sensors in innate immune cells recognize and respond to cell-death signatures. We also highlight molecular targets of the innate immune response for potential therapeutic development.
先天免疫、细胞死亡和炎症是健康和疾病的多个方面的基础。在感知病原体、病原体相关分子模式或损伤相关分子模式时，先天免疫系统会激活裂解性、炎症性细胞死亡，如细胞焦亡和 PANoptosis。这些基因定义的、受调控的细胞死亡途径不仅有助于宿主抵御传染病，还促进导致癌症和炎症性疾病的病理表现。近年来，我们对潜在机制的理解迅速发展。然而，垂死细胞、细胞尸骸及其释放的细胞因子、趋化因子和炎症信号分子如何被先天免疫细胞进一步感知，以及它们对进一步放大炎症、触发抗原呈递和激活适应性免疫的贡献尚不清楚。在这里，我们讨论先天免疫细胞中的模式识别和 PANoptosome 传感器如何识别和响应细胞死亡特征。我们还强调了先天免疫反应的分子靶标，以用于潜在的治疗开发。
