Molecular control of activation and priming in macrophages

In tissues, macrophages are exposed to metabolic, homeostatic and immune-regulatory signals of local or systemic origin that influence their basal functions and responses to danger signals. Signal transduction pathways regulated by extracellular signals are coupled to distinct sets of broadly expressed stimulus-regulated transcription factors whose ability to elicit gene expression changes is influenced by the accessibility of their DNA binding sites in the macrophage genome. In turn, accessibility of macrophage-specific transcriptional regulatory elements (enhancers and promoters) is specified by transcription factors that determine the macrophage lineage or impose their tissue-specific properties. Here, we review recent findings that advance our understanding of mechanisms underlying priming and signal-dependent activation of macrophages, and discuss the impact of genetic variation on these processes