@article{22077,
  keywords = {25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Antimicrobial Cationic Peptides, Cells, Cultured, Humans, Interleukin-10, Interleukin-1beta, leprosy, Leprosy, lepromatous, Leprosy, Tuberculoid, MicroRNAs, Monocytes, tratamento, Signal Transduction, Toll-Like Receptor 1, Toll-Like Receptor 2, Vitamin D, Beta-Defensins},
  author = {Sarno E and Modlin RL and Rea T and Liu PT and Graeber T and Teles R and Wheelwright M and Edfeldt K and Ferguson B and Komisopoulou E and Mehta M and Vazirnia A},
  title = {MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy.},
  abstract = {<p>Leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a spectrum of clinical presentations that correlate with host immune responses. Here we identified 13 miRNAs that were differentially expressed in the lesions of subjects with progressive lepromatous (L-lep) versus the self-limited tuberculoid (T-lep) disease. Bioinformatic analysis revealed a significant enrichment of L-lep-specific miRNAs that preferentially target key immune genes downregulated in L-lep versus T-lep lesions. The most differentially expressed miRNA in L-lep lesions, hsa-mir-21, was upregulated in Mycobacterium leprae-infected monocytes. By directly downregulating Toll-like receptor 2/1 heterodimer (TLR2/1)-induced CYP27B1 and IL1B expression as well as indirectly upregulating interleukin-10 (IL-10), hsa-mir-21 inhibited expression of the genes encoding two vitamin D-dependent antimicrobial peptides, CAMP and DEFB4A. Conversely, knockdown of hsa-mir-21 in M. leprae-infected monocytes enhanced expression of CAMP and DEFB4A and restored TLR2/1-mediated antimicrobial activity against M. leprae. Therefore, the ability of M. leprae to upregulate hsa-mir-21 targets multiple genes associated with the immunologically localized disease form, providing an effective mechanism to escape from the vitamin D-dependent antimicrobial pathway.</p>},
  year = {2012},
  journal = {Nature medicine},
  volume = {18},
  pages = {267-73},
  month = {2012 Jan 29},
  publisher = {Nature Publishing Company},
  address = {New York },
  issn = {1546-170X},
  doi = {10.1038/nm.2584},
  language = {eng},
}