HIF-1alpha: a master regulator of innate host defenses?
In the days following infection, when the human body develops and refines antibodies and prepares to mount an adaptive immune response, the bulwark of innate host defense against microbial infection is the polymorphonuclear leukocyte (PMN). PMNs seek out, identify, engulf, and sterilize invading microbes using both O2-dependent and O2-independent antimicrobial systems. A decrease in PMN numbers or function caused by immunosuppression or disease increases the risk of infection. In this issue of the JCI, Peyssonnaux et al. identify a novel and essential role for hypoxia-inducible factor-1alpha in regulating several important PMN functions relevant to host defense, including transcription of cationic antimicrobial polypeptides and induction of NO synthase.
Zarember
Kol A
KA
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Malech
Harry L
HL
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D016922:Cellular Senescence; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007113:Immunity, Innate; D007239:Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D014157:Transcription Factors / Q000276:immunology* / Q000502:physiology; D014158:Transcription, Genetic
D023181:Antimicrobial Cationic Peptides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D019001:Nitric Oxide Synthase