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|Title:||Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA||Authors:||Cervantes, Jorge L.
Lorenzini, Paolo A.
Salazar, Juan C.
|Keywords:||Science::Biological sciences||Issue Date:||2019||Source:||Cervantes, 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. https://dx.doi.org/10.1016/j.tube.2019.04.021||Project:||MOE2013-T2-1-101
|Journal:||Tuberculosis||Abstract:||Mycobacterium 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.||URI:||https://hdl.handle.net/10356/150639||ISSN:||1472-9792||DOI:||10.1016/j.tube.2019.04.021||Rights:||© 2019 Elsevier Ltd. All rights reserved.||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||SBS Journal Articles|
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