Microglia are brain-resident macrophages forming the first active immune barrier in the central nervous system. They fulfill multiple functions across development and adulthood and under disease conditions. Current understanding revolves around microglia acquiring distinct phenotypes upon exposure to extrinsic cues in their environment. However, emerging evidence suggests that microglia display differences in their functions that are not exclusively driven by their milieu, rather by the unique properties these cells possess. This microglial intrinsic heterogeneity has been largely overlooked, favoring the prevailing view that microglia are a single-cell type endowed with spectacular plasticity, allowing them to acquire multiple phenotypes and thereby fulfill their numerous functions in health and disease. Here, we review the evidence that microglia might form a community of cells in which each member (or "subtype") displays intrinsic properties and performs unique functions. Distinctive features and functional implications of several microglial subtypes are considered, across contexts of health and disease. Finally, we suggest that microglial subtype categorization shall be based on function and we propose ways for studying them. Hence, we advocate that plasticity (reaction states) and diversity (subtypes) should both be considered when studying the multitasking microglia.

中文翻译：

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小胶质细胞亚型：小胶质细胞群落内的多样性。

小胶质细胞是驻留在大脑中的巨噬细胞，在中枢神经系统中形成第一个活性免疫屏障。它们在疾病的发展和成年期都具有多种功能。当前的理解围绕着小胶质细胞暴露于环境中的外在线索而获得不同的表型。但是，新出现的证据表明，小胶质细胞显示出功能上的差异，这些差异并非仅由其环境所驱动，而是由这些细胞所具有的独特特性所驱动。这种小胶质细胞固有的异质性已被大大忽略，支持一种普遍的观点，即小胶质细胞是一种具有惊人可塑性的单细胞类型，可以使它们获得多种表型，从而在健康和疾病中发挥其众多功能。这里，我们审查了小胶质细胞可能形成细胞群落的证据，其中每个成员（或“亚型”）均显示内在特性并执行独特的功能。在健康和疾病的背景下，考虑了几种小胶质细胞亚型的独特特征和功能含义。最后，我们建议小胶质细胞亚型的分类应基于功能，并提出研究方法。因此，我们提倡在研究多任务小胶质细胞时应同时考虑可塑性（反应状态）和多样性（亚型）。最后，我们建议小胶质细胞亚型的分类应基于功能，并提出研究方法。因此，我们提倡在研究多任务小胶质细胞时应同时考虑可塑性（反应状态）和多样性（亚型）。最后，我们建议小胶质细胞亚型的分类应基于功能，并提出研究方法。因此，我们提倡在研究多任务小胶质细胞时应同时考虑可塑性（反应状态）和多样性（亚型）。