Macrophages are first responders for the immune system. In this role, they have both effector functions for neutralizing pathogens and sentinel functions for alerting other immune cells of diverse pathologic threats, thereby initiating and coordinating a multipronged immune response. Macrophages are distributed throughout the body—they circulate in the blood, line the mucosal membranes, reside within organs, and survey the connective tissue. Several reviews have summarized their diverse roles in different physiological scenarios and in the initiation or amplification of different pathologies. In this review, we propose that both the effector and the sentinel functions of healthy macrophages rely on three hallmark properties: response specificity, context dependence, and stimulus memory. When these hallmark properties are diminished, the macrophage's biological functions are impaired, which in turn results in increased risk for immune dysregulation, manifested by immune deficiency or autoimmunity. We review the evidence and the molecular mechanisms supporting these functional hallmarks.

中文翻译：

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健康巨噬细胞反应的功能标志：其调节基础和疾病相关性

巨噬细胞是免疫系统的第一反应者。在这个角色中，它们既具有中和病原体的效应器功能，又具有警告其他免疫细胞多种病理威胁的前哨功能，从而启动和协调多管齐下的免疫反应。巨噬细胞遍布全身——它们在血液中循环，排列在粘膜上，驻留在器官内，并检查结缔组织。一些评论总结了它们在不同生理情况以及不同病理的引发或放大中的不同作用。在这篇综述中，我们提出健康巨噬细胞的效应器和前哨功能都依赖于三个标志特性：反应特异性、环境依赖性和刺激记忆。当这些标志特性减弱时，巨噬细胞的生物学功能就会受损，进而导致免疫失调的风险增加，表现为免疫缺陷或自身免疫。我们回顾了支持这些功能标志的证据和分子机制。