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Alveolar macrophages from patients with tuberculosis exhibit reduced capacity of restricting growth of Mycobacterium tuberculosis: a pilot study of vitamin D stimulation in vitro

Artikel i vetenskaplig tidskrift
Författare Persson H. Lennart
Daniel Eklund
Marie Larsson
Amanda Welin
Jakob Paues
Jonna Idh
Sven Goran Fransson
Olle Stendahl
Maria Lerm
Thomas Schon
Publicerad i Microbiology Discovery
Volym 1
Sidor article number 6
ISSN 2052-6180
Publiceringsår 2013
Publicerad vid Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Sidor article number 6
Språk en
Länkar dx.doi.org/10.7243/2052-6180-1-6
Ämnesord Alveolar macrophages, bronchoalveolar lavage, cytokines, H37Rv, tuberculosis
Ämneskategorier Klinisk bakteriologi, Medicinsk mikrobiologi, Immunbiologi

Sammanfattning

Background: The role of vitamin D supplementation as adjuvant treatment of tuberculosis (TB) has lately attracted increasing interest. Our aim was to investigate the capacity of alveolar macrophages (AMs) from patients with or without exposure to TB to control intracellular growth of virulent Mycobacterium tuberculosis (Mtb). Methods: AMs were freshly harvested from the bronchoalveolar lavage fluid of 7 patients with a history of TB (4 patients with previous TB and 3 patients with current TB) and 4 non-TB subjects. The H37Rv strain, genetically modified to express Vibrio harveyi luciferase, was used to determine the growth of Mtb by luminometry in the AMs from study subjects. Cytokine levels in culture supernatants were determined using a flow cytometry-based bead array technique. Results: AMs from patients with a TB history were less efficient in restricting Mtb growth. Stimulation with 100 nM1, 25-dihydroxyvitamin D (1,25D3) did not significantly influence the capacity of AMs from any study subjects to control the infection. Out of the cytokines evaluated (TNF-α, IL-1β, IL-10 and IL-12p40) only TNF-α demonstrated detectable levels in culture supernatants, but did not respond to stimulation with 1,25D3. Conclusions: We conclude that AMs of TB-patients show reduced ability to control mycobacterial growth in vitro, and, that AMs in this pilot study do no respond to 1, 25D3-stimulation. The former observation supports the concept that innate immunity is crucial for the control of TB infection.

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