HIF-1α sets the activation tempo of inflammatory macrophages.

Hypoxia-inducible factor 1a (HIF-1α) sustains cell survival and metabolic adaptations under low-oxygen conditions and supports metabolic reprogramming of pro-inflammatory macrophages. In this issue of Molecular Cell, Davanzo and colleagues1 uncover a HIF-1α-dependent biphasic regulatory program of macrophage activation in response to inflammatory cues and delineate its dynamic role in shaping antimicrobial defenses.