Nature Reviews Immunology 9, 609-617 (September 2009) | doi:10.1038/nri2607

Article series: Tissue-specific immune responses

Interdependence of hypoxic and innate immune responses

Victor Nizet1,2 & Randall S. Johnson1  About the authors


Hypoxia-inducible factor (HIF) is an important transcriptional regulator of cell metabolism and the adaptation to cellular stress caused by oxygen deficiency (hypoxia). Phagocytic cells have an essential role in innate immune defence against pathogens and this is a battle that takes place mainly in the hypoxic microenvironments of infected tissues. It has now become clear that HIF promotes the bactericidal activities of phagocytic cells and supports the innate immune functions of dendritic cells, mast cells and epithelial cells. In response to microbial pathogens, HIF expression is upregulated through pathways involving the key immune response regulator nuclear factor-kappaB, highlighting an interdependence of the innate immune and hypoxic responses to infection and tissue damage. In turn, HIF-driven innate immune responses have important consequences for both the pathogen and the host, such that the tissue microenvironment fundamentally influences susceptibility to infectious disease.

Author affiliations

  1. Department of Pediatrics, 9500 Gilman Drive, La Jolla, California 92093, USA
  2. Skaggs School of Pharmacy and Pharmaceutical Sciences, 9500 Gilman Drive, La Jolla, California 92093, USA
  3. Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
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