Hypoxia-inducible factor-1α regulation of myeloid cells.


Hematopoietic myeloblasts give rise to macrophages, dendritic cells, and neutrophils. Circulating myeloid cells detect invading microbes using pattern recognition receptors and subsequently orchestrate an innate immune response to contain and kill the pathogens. This innate immune response establishes an inflammatory niche characterized by hypoxia due to host and pathogen factors. Hypoxia-inducible factor (HIF) transcription factors are the primary regulators of the myeloid response to hypoxia. In particular, HIF-1α is a critical hub that integrates hypoxic and immunogenic signals during infection or inflammation. Hypoxia induces HIF-1α stabilization, which drives metabolic and phenotypic reprogramming of myeloid cells to maximize antimicrobial potential. HIF-1α activity in myeloid-derived cells enhances the host response to infection, but may also play a role in pathogenic inflammatory processes, such as atherosclerosis. In this review, we summarize recent advances that have elucidated the mechanism by which myeloid cells regulate HIF-1α activity and, in turn, how HIF-1α shapes myeloid cell function.