02598nas a2200469   4500000000100000008004100001260005400042653004500096653003600141653002000177653001100197653001900208653002200227653001200249653002500261653002500286653001400311653001400325653001500339653002400354653002500378653002500403653001400428653001900442100001200461700001400473700001000487700001100497700001400508700001200522700001800534700001400552700001500566700001900581700001200600700001500612245008200627300001100709490000700720520138700727022001402114       2012                            d  c2012 Jan 29bNature Publishing CompanyaNew York 10a25-Hydroxyvitamin D3 1-alpha-Hydroxylase10aAntimicrobial Cationic Peptides10aCells, Cultured10aHumans10aInterleukin-1010aInterleukin-1beta10aleprosy10aLeprosy, lepromatous10aLeprosy, Tuberculoid10aMicroRNAs10aMonocytes10atratamento10aSignal Transduction10aToll-Like Receptor 110aToll-Like Receptor 210aVitamin D10aBeta-Defensins1 aSarno E1 aModlin RL1 aRea T1 aLiu PT1 aGraeber T1 aTeles R1 aWheelwright M1 aEdfeldt K1 aFerguson B1 aKomisopoulou E1 aMehta M1 aVazirnia A00aMicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy.  a267-730 v183 a<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>  a1546-170X