title: Hypoxia triggers the expression of human β defensin 2 and antimicrobial activity against Mycobacterium tuberculosis in human macrophages.
abstract: Low oxygen tension is a metabolic hallmark of chronic infection. To investigate the influence of hypoxia on macrophage biology, we analyzed the interaction between the intracellular pathogen Mycobacterium tuberculosis and primary human macrophages. Although the metabolic activity of extracellular M. tuberculosis was reduced at oxygen levels between 0.5 and 10%, the bacilli remained viable throughout the 4 d of culture. Phagocytosis of virulent M. tuberculosis and the pathogen-induced release of inflammatory cytokines by macrophages were not affected by oxygen levels as low as 1%. However, we detected the upregulation of an antimicrobial effector pathway mediated by the vitamin D receptor and human β defensin 2. This finding was functionally relevant, because intracellular mycobacterial growth was inhibited by 58 ± 8% at 1% O(2). We conclude that a hypoxic microenvironment, which is characteristic of infected tissue, supports the efficacy of antimicrobial immunity, in part by the upregulation of the antimicrobial peptide human β defensin 2.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Ulm, D-89081 Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nickel
authors.forename: Martin
authors.initials: M
authors.lastname: Busch
authors.forename: Daniel
authors.initials: D
authors.lastname: Mayer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hagemann
authors.forename: Valeska
authors.initials: V
authors.lastname: Knoll
authors.forename: Steffen
authors.initials: S
authors.lastname: Stenger
mesh_terms: D015687:Cell Hypoxia; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis; D061251:Primary Cell Culture; D018167:Receptors, Calcitriol / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; C106641:DEFB4A protein, human; D018167:Receptors, Calcitriol; D023083:beta-Defensins; D010100:Oxygen