Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
College of Applied Medical Science, Taibah University, Madina, Saudi Arabia.
Nat Commun. 2022 Nov 25;13(1):7272. doi: 10.1038/s41467-022-34935-w.
Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.
肺泡巨噬细胞（AM）维持着肺部的内环境稳定。除了抵御吸入的病原体和有害炎症外，AM 还维持着肺表面活性剂的内环境稳定，这是一种防止肺泡蛋白沉积症的重要肺部功能。AM 和肺实质细胞之间传递的信号协调了这些特殊功能。然而，指导 AM 代谢内环境稳定的机制在很大程度上仍未被揭示。我们发现 NK 细胞相关受体 NKR-P1B 由 AM 表达，对代谢编程至关重要。由于 AM 数量随年龄增长而减少以及富含脂质的 AM 的形成，Nkrp1b 小鼠易感染肺炎球菌。Nkrp1b 小鼠的 AM 显示出表面活性剂脂质摄取增加但代谢缺陷。我们发现 AM 和肺泡 II 型上皮细胞之间存在一种依赖于上皮细胞 Clr-g 表达的物理联系。这些发现表明 NKR-P1B：Clr-g 信号轴在 AM-上皮细胞通讯中对于维持 AM 中的代谢至关重要。
