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dc.contributor.authorCervantes, Jorge L.en_US
dc.contributor.authorOak, Estheren_US
dc.contributor.authorGarcia, Johnen_US
dc.contributor.authorLiu, Hongfeien_US
dc.contributor.authorLorenzini, Paolo A.en_US
dc.contributor.authorBatra, Deepikaen_US
dc.contributor.authorChhabra, Arvinden_US
dc.contributor.authorSalazar, Juan C.en_US
dc.contributor.authorRoca, Xavieren_US
dc.identifier.citationCervantes, J. L., Oak, E., Garcia, J., Liu, H., Lorenzini, P. A., Batra, D., Chhabra, A., Salazar, J. C. & Roca, X. (2019). Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA. Tuberculosis, 116, S131-S137.
dc.description.abstractMycobacterium tuberculosis (Mtb) is a facultative intracellular pathogen that infects macrophages where it avoids elimination by interfering with host defense mechanisms, including phago-lysosome fusion. Endosomal Toll-like receptors (TLRs) generate Type I Interferons (IFNs), which are associated with active tuberculosis (TB). We aimed to explore if DNA from different Mtb lineages lead to differences in the inflammatory response of human monocytic/macrophage cells. THP-1 cells which express two inducible reporter constructs for interferons (IFNs) as well as for NF-κB, were stimulated via endosomal delivery of Mtb DNA as a nanocomplex with PEI. DNA from different Mtb phylogenetic lineages elicited differential inflammatory responses in human macrophages. An initial relatively weak IRF-mediated response to DNA from HN878 and H37Rv increased if the cells were pre-treated with Vitamin D (Vit D) for 72 h. RNAseq of THP-1 under different transformation conditions showed that pre-treatment with Vit D upregulated several TLR9 variants, as well as genes involved in inflammatory immune response to infection, immune cell activation, Type I IFN regulation, and regulation of inflammation. Vit D appears to be important in increasing low IRF responses to DNA from certain lineages of Mtb. Variations in the IRF-mediated response to DNA derived from different Mtb genotypes are potentially important in the pathogenesis of tuberculosis since Type I IFN responses are associated with active disease. The role of Vit D in these responses could also translate into future therapeutic approaches.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.relationARC 45/13en_US
dc.rights© 2019 Elsevier Ltd. All rights reserved.en_US
dc.subjectScience::Biological sciencesen_US
dc.titleVitamin D modulates human macrophage response to Mycobacterium tuberculosis DNAen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.schoolInterdisciplinary Graduate School (IGS)en_US
dc.contributor.researchNanyang Institute of Technology in Health and Medicineen_US
dc.subject.keywordsMycobacterium Tuberculosisen_US
dc.subject.keywordsType I IFNsen_US
dc.description.acknowledgementThis work was supported by NIAID grants AI0901656 (JS) and CCMC Arrison and Burr Curtis Research funds (JS). XR acknowledges funding from Academic Research Fund Tier 2 MOE2013-T2-1-101 (ARC 45/13) from Singapore's Ministry of Education. The funders played no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
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