HIF-1α:: 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 O-2-dependent and O-2-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-1 alpha in regulating several important PMN functions relevant to host defense, including transcription of cationic antimicrobial polypeptides and induction of NO synthase (see the related article beginning on page 1806).