Hypoxia-Inducible Factor (HIF) as a Pharmacological Target for Prevention and Treatment of Infectious Diseases

In the present era of ever-increasing antibiotic resistance and increasingly complex and immunosuppressed patient populations, physicians and scientists are seeking novel approaches to battle difficult infectious disease conditions. Development of a serious infection implies a failure of innate immune capabilities in the patient, and one may consider whether pharmacological strategies exist to correct and enhance innate immune cell function. Hypoxia-inducible factor-1 (HIF-1), the central regulator of the cellular response to hypoxic stress, has recently been recognized to control the activation state and key microbicidal functions of immune cells. HIF-1 boosting drugs are in clinical development for anemia and other indications, and could be repositioned as infectious disease therapeutics. With equal attention to opportunities and complexities, we review our current understanding of HIF-1 regulation of microbial host-pathogen interactions with an eye toward future drug development.