E-GEOD-8921 - Transcription profiling of human TLR2/1 stimulated human monocytes with the Mycobacterium tuberculosis derived 19kDa lipopeptide reveals Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response
Submitted on 30 August 2007, released on 17 June 2008, last updated on 27 March 2012
In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection. Experiment Overall Design: The monocyte microarrays were generated using primary human monocytes stimulated with a TLR2/1L or media at 0, 3, 6, 12, 24 hour timepoints. A total of 10 donors were used with time 0 h samples prepared for each. For time points, we used cells from 4 of the 10 donors to prepare media and TLR2/1-stimulated samples. Experiment Overall Design: Dendritic cells were generated by culturing primary human monocytes with GM-CSF (800 U/ml) and IL-4 (1000 U/ml) for 7 days. The cells were then harvested and recultured for 12 hours with TLR2/1L or media. A total of four donors were used. Experiment Overall Design: See manuscript for specific details on data analysis and experimental design and reagents.
transcription profiling by array, unknown experiment type
Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Philip T Liu, Steffen Stenger, Huiying Li, Linda Wenzel, Belinda H Tan, Stephan R Krutzik, Maria Teresa Ochoa, Jürgen Schauber, Kent Wu, Christoph Meinken, Diane L Kamen, Manfred Wagner, Robert Bals, Andreas Steinmeyer, Ulrich Zügel, Richard L Gallo, David Eisenberg, Martin Hewison, Bruce W Hollis, John S Adams, Barry R Bloom, Robert L Modlin. Science 311(5768):1770-3 (2006)