title: Vitamin D enhances IL-1β secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients.
abstract: The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MTB), the bacterium responsible for tuberculosis (TB), has rekindled the interest in the role of nutritional supplementation of micronutrients, such as vitamin D, as adjuvant treatment. Here, the growth of virulent MTB in macrophages obtained from the peripheral blood of patients with and without TB was studied. The H37Rv strain genetically modified to express Vibrio harveyi luciferase was used to determine the growth of MTB by luminometry in the human monocyte-derived macrophages (hMDMs) from study subjects. Determination of cytokine levels in culture supernatants was performed using a flow cytometry-based bead array technique. No differences in intracellular growth of MTB were observed between the different study groups. However, stimulation with 100nM 1,25-dihydroxyvitamin D significantly enhanced the capacity of hMDMs isolated from TB patients to control the infection. This effect was not observed in hMDMs from the other groups. The interleukin (IL)-1β and IL-10 release by hMDMs was clearly increased upon stimulation with 1,25-dihydroxyvitamin D. Furthermore, the 1,25-dihydroxyvitamin D stimulation also led to elevated levels of TNF-α (tumor necrosis factor-alpha) and IL-12p40. It was concluded that vitamin D triggers an inflammatory response in human macrophages with enhanced secretion of cytokines, as well as enhancing the capacity of hMDMs from patients with active TB to restrict mycobacterial growth.
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eklund
authors.affiliation: Division of Pulmonary Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Sweden; Department of Respiratory Medicine UHL, Centre of Surgery and Oncology, Linköping University Hospital, SE-581 85 Linköping, Sweden.
authors.forename: Hans Lennart
authors.initials: HL
authors.lastname: Persson
authors.affiliation: Division of Clinical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden; Phagocyte Research Laboratory, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden.
authors.forename: Amanda
authors.initials: A
authors.lastname: Welin
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Jonna
authors.initials: J
authors.lastname: Idh
authors.affiliation: Division of Infectious Diseases, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Paues
authors.affiliation: Division of Radiology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Sven-Göran
authors.initials: SG
authors.lastname: Fransson
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Stendahl
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden; Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, SE-391 85 Kalmar, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schön
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden; Center for Infectious Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden. Electronic address: maria.lerm@liu.se.
authors.forename: Maria
authors.initials: M
authors.lastname: Lerm
keywords: Human macrophages; IL-1β; Intracellular growth; TB patients; Vitamin D