Division of Medicine, University College London, London, UK.
Centre of Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Immunol Lett. 2021 Feb;230:1-10. doi: 10.1016/j.imlet.2020.12.003. Epub 2020 Dec 10.
Ageing is a global burden. Increasing age is associated with increased incidence of infections and cancer and decreased vaccine efficacy. This increased morbidity observed with age, is believed to be due in part to a decline in adaptive immunity, termed immunosenescence. However not all aspects of immunity decrease with age as ageing presents with systemic low grade chronic inflammation, characterised by elevated concentrations of mediators such as IL-6, TNFα and C Reactive protein (CRP). Inflammation is a strong predictor of morbidity and mortality, and chronic inflammation is known to be detrimental to a functioning immune system. Although the source of the inflammation is much discussed, the key cells which are believed to facilitate the inflammageing phenomenon are the monocytes and macrophages. In this review we detail how macrophage and monocyte phenotype and function change with age. The impact of ageing on macrophages includes decreased phagocytosis and immune resolution, increased senescent-associated markers, increased inflammatory cytokine production, reduced autophagy, and a decrease in TLR expression. With monocytes there is an increase in circulating CD16 monocytes, decreased type I IFN production, and decreased efferocytosis. In conclusion, we believe that monocytes and macrophages contribute to immunosenescence and inflammageing and as a result have an important role in defective immunity with age.
衰老是一个全球性的负担。随着年龄的增长，感染和癌症的发病率增加，疫苗的效果降低。这种随着年龄增长而观察到的发病率增加，部分归因于适应性免疫的下降，称为免疫衰老。然而，并非所有免疫方面都会随着年龄的增长而下降，因为衰老会出现全身性低度慢性炎症，其特征是介质浓度升高，如白细胞介素-6、肿瘤坏死因子-α和 C 反应蛋白 (CRP)。炎症是发病率和死亡率的强烈预测因子，已知慢性炎症对免疫系统的功能有害。尽管炎症的来源有很多讨论，但被认为促进炎症衰老现象的关键细胞是单核细胞和巨噬细胞。在这篇综述中，我们详细描述了巨噬细胞和单核细胞表型和功能随年龄的变化。衰老对巨噬细胞的影响包括吞噬作用和免疫缓解能力降低、衰老相关标志物增加、炎症细胞因子产生增加、自噬减少以及 TLR 表达减少。对于单核细胞，循环 CD16 单核细胞增加，I 型干扰素产生减少，吞噬作用减少。总之，我们认为单核细胞和巨噬细胞有助于免疫衰老和炎症衰老，因此在年龄相关的免疫缺陷中起着重要作用。
