Pharmacologic augmentation of hypoxia-inducible factor-1alpha with mimosine boosts the bactericidal capacity of phagocytes.
Hypoxia-inducible factor (HIF)-1alpha is activated on exposure to bacterial pathogens and regulates the innate immune functions of phagocytes. We show here that the HIF-1alpha agonist mimosine can boost the capacity of human phagocytes and whole blood to kill the leading pathogen Staphylococcus aureus in a dose-dependent fashion and reduce the lesion size in a murine model of S. aureus skin infection. This provides the first proof of principle for a novel approach to the treatment of bacterial infection by pharmacologically augmenting the host phagocytic function.
Zinkernagel
Annelies S
AS
1Division of Pediatric Pharmacology and Drug Discovery, School of Medicine, University of California, San Diego, La Jolla 92093-0687, USA.
Peyssonnaux
Carole
C
Johnson
Randall S
RS
Nizet
Victor
V
D000818:Animals; D001770:Blood Bactericidal Activity; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000819:agonists* / Q000276:immunology*; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D008898:Mimosine / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D016897:Respiratory Burst; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D020298:U937 Cells
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008898:Mimosine