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    Increased vitamin D receptor expression from macrophages after stimulation with M. tuberculosis among persons who have recovered from extrapulmonary tuberculosis

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    Author
    Fiske, C.T.
    Blackman, A.
    Maruri, F.
    Date
    2019
    Journal
    BMC Infectious Diseases
    Publisher
    BioMed Central Ltd.
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1186/s12879-019-3958-7
    Abstract
    Background: Independent of HIV infection, extrapulmonary TB (EPTB) risk is increased in women, persons of black race or foreign birth, and by genetic variants in vitamin D receptor (VDR), interleukin-1 beta (IL-1β), and toll-like receptor (TLR)-2; functional correlates are unclear. We evaluated macrophage expression of VDR, TLR2, cathelicidin, and TNF-α, and production of IL-1β in HIV-seronegative persons with previous EPTB, previous pulmonary TB, latent M. tuberculosis infection, and uninfected TB contacts. Persons with previous pleural TB were excluded due to enhanced immune responses at the site of disease. Methods: Macrophages were stimulated with TLR-2 agonist M. tuberculosis lipoprotein (LpqH), live and gamma-irradiated M. tuberculosis. Results: M. tuberculosis – infected macrophages from persons with previous EPTB had increased VDR expression (29.17 relative value unit increase in median expression vs. uninfected contacts, after adjusting for foreign-born status; P = 0.02). Macrophages from persons with previous EPTB had a 38.88 μg/mL increase in median IL-1β production after stimulation with LpqH compared to uninfected contacts (P = 0.01); the effect was similar (44.99 μg/mL) but not statistically significant after controlling for foreign-born status. Median 25-hydroxyvitamin D levels were low but not significantly different between groups. Conclusions: There was increased macrophage expression of VDR after stimulation with live M. tuberculosis in persons with previous extrapulmonary TB. If post-treatment VDR expression reflects expression prior to disease, it may identify persons at risk for extrapulmonary TB. Copyright 2019 The Author(s).
    Sponsors
    National Institutes of Health (K23AI091692 (CTF), K24AI065298 (AB, TRS), Potts Memorial Foundation.
    Keyword
    Extrapulmonary tuberculosis
    Interleukin-1 beta
    M. Tuberculosis
    Toll-like receptor 2
    Vitamin D receptor
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065123565&doi=10.1186%2fs12879-019-3958-7&partnerID=40&md5=d44fc43999c442da19576b5dd485af28; http://hdl.handle.net/10713/10663
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12879-019-3958-7
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