Vitamin D enhances IL-1β secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients

Daniel Eklund; Hans Lennart Persson; Marie Larsson; Amanda Welin; Jonna Idh; Jakob Paues; Sven-Göran Fransson; Olle Stendahl; Thomas Schön; Maria Lerm

doi:10.1016/j.ijmyco.2012.11.001

Vitamin D enhances IL-1β secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients

Int J Mycobacteriol. 2013 Mar;2(1):18-25. doi: 10.1016/j.ijmyco.2012.11.001. Epub 2012 Dec 20.

Authors

Affiliations

¹ Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
² 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.
³ Division of Clinical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
⁴ 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.
⁵ Division of Infectious Diseases, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
⁶ Division of Radiology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
⁷ 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.
⁸ 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.

PMID: 26785783
DOI: 10.1016/j.ijmyco.2012.11.001

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.

Keywords: Human macrophages; IL-1β; Intracellular growth; TB patients; Vitamin D.