Journal of Molecular Medicine

, Volume 96, Issue 12, pp 1293–1306 | Cite as

Hypoxia-inducible factor-1α regulation of myeloid cells

  • C. L. StothersEmail author
  • L. Luan
  • B. A. Fensterheim
  • J. K. Bohannon


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.


Myeloid HIF Immunometabolism Hypoxia Inflammation 





ATP-binding cassette subfamily a member 1


Adenosine triphosphate


C-C chemokine receptor


Cluster of differentiation


Mitochondrial citrate carrier


Clustered regularly interspaced short palindromic repeats


Dendritic cells


Dimethyloxallyl glycine


Dextran sodium sulfate


Fatty acid oxidation


Protein factor inhibiting HIF-1


Glucose transporter 1


L-gulono-γ-lactone oxidase


Hypoxia-inducible factor


HIF response elements


Inflammatory bowel disease




Iκb kinase beta




Inducible nitric oxide synthase


Inhibitor of nuclear factor-kappa B


Krüppel-like factor 2


Low-density lipoprotein




Major histocompatibility complex


Macrophage inflammatory protein-1β


Monophosphoryl lipid A


Mechanistic target of rapamycin


Neutrophil extracellular traps


Nuclear factor of kappa B


Nitric oxide


oxidized low-density lipoprotein


Prolyl-4-hydoxylase domain enzymes


Phosphoinositide 3-kinase


Pyruvate kinase


Pyruvate kinase muscle isoenzyme


Pentose phosphate pathway


Von Hippel-Lindau E3 ubiquitin ligase


Reactive nitrogen species


Reactive oxygen species


Succinate dehydrogenase


Sirtuin deacetylase 1 and 2

TCA cycle

Tricarboxylic acid cycle


T helper cell type 1 and 2


Toll-like receptor


Regulatory T cell


Vascular endothelial growth factor


Funding information

This work was supported by the NIH grants R01 GM121711 (to JKB) and T32 GM007347 Medical Scientist Training Program Grant (to CLS and BAF).

Compliance with ethical standards

Conflicts of interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • C. L. Stothers
    • 1
    Email author
  • L. Luan
    • 2
  • B. A. Fensterheim
    • 1
  • J. K. Bohannon
    • 2
  1. 1.Department of Pathology, Microbiology, and ImmunologyVanderbilt University School of MedicineNashvilleUSA
  2. 2.Department of AnesthesiologyVanderbilt University Medical CenterNashvilleUSA

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