Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA
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 wi...
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| Format: | Journal Article |
| Language: | English |
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2021
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| Online Access: | https://hdl.handle.net/10356/150639 |
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| author | Cervantes, Jorge L. Oak, Esther Garcia, John Liu, Hongfei Lorenzini, Paolo A. Batra, Deepika Chhabra, Arvind Salazar, Juan C. Roca, Xavier |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Cervantes, Jorge L. Oak, Esther Garcia, John Liu, Hongfei Lorenzini, Paolo A. Batra, Deepika Chhabra, Arvind Salazar, Juan C. Roca, Xavier |
| author_sort | Cervantes, Jorge L. |
| collection | NTU |
| description | 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. |
| first_indexed | 2025-02-19T03:15:46Z |
| format | Journal Article |
| id | ntu-10356/150639 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:15:46Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1506392021-08-03T13:57:00Z Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA Cervantes, Jorge L. Oak, Esther Garcia, John Liu, Hongfei Lorenzini, Paolo A. Batra, Deepika Chhabra, Arvind Salazar, Juan C. Roca, Xavier School of Biological Sciences Interdisciplinary Graduate School (IGS) Nanyang Institute of Technology in Health and Medicine Science::Biological sciences Mycobacterium Tuberculosis Type I IFNs 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. Ministry of Education (MOE) This 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. 2021-08-03T13:57:00Z 2021-08-03T13:57:00Z 2019 Journal Article 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 1472-9792 https://hdl.handle.net/10356/150639 10.1016/j.tube.2019.04.021 31085128 2-s2.0-85065424588 116 S131 S137 en MOE2013-T2-1-101 ARC 45/13 Tuberculosis © 2019 Elsevier Ltd. All rights reserved. |
| spellingShingle | Science::Biological sciences Mycobacterium Tuberculosis Type I IFNs Cervantes, Jorge L. Oak, Esther Garcia, John Liu, Hongfei Lorenzini, Paolo A. Batra, Deepika Chhabra, Arvind Salazar, Juan C. Roca, Xavier Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA |
| title | Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA |
| title_full | Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA |
| title_fullStr | Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA |
| title_full_unstemmed | Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA |
| title_short | Vitamin D modulates human macrophage response to Mycobacterium tuberculosis DNA |
| title_sort | vitamin d modulates human macrophage response to mycobacterium tuberculosis dna |
| topic | Science::Biological sciences Mycobacterium Tuberculosis Type I IFNs |
| url | https://hdl.handle.net/10356/150639 |
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