02437nas a2200565   4500000000100000008004100001260001600042653004500058653003600103653001100139653002000150653002100170653001900191653002500210653002500235653002400260653001400284653002500298653001900323653002600342653001800368653001700386653001800403653001900421100001200440700001400452700001500466700001500481700001300496700001100509700001900520700002000539700001100559700001100570700001200581700001000593700001400603700001200617700001400629700001300643700001400656700001200670700001200682700001400694245009800708300001200806490000800818520103100826022001401857       2013                            d  c2013 Mar 2210a25-Hydroxyvitamin D3 1-alpha-Hydroxylase10aAntimicrobial Cationic Peptides10aHumans10aInterferon-beta10aInterferon-gamma10aInterleukin-1010aLeprosy, lepromatous10aLeprosy, Tuberculoid10aMicrobial Viability10aMonocytes10aMycobacterium leprae10aRNA, Messenger10aReceptors, Calcitriol10aTranscriptome10aTuberculosis10aUp-Regulation10aBeta-Defensins1 aTeles R1 aGraeber T1 aKrutzik SR1 aMontoya DJ1 aSchenk M1 aLee DJ1 aKomisopoulou E1 aKelly-Scumpia K1 aChun R1 aIyer S1 aSarno E1 aRea T1 aHewison M1 aAdams J1 aPopper SJ1 aRelman D1 aStenger S1 aBloom B1 aCheng G1 aModlin RL00aType I interferon suppresses type II interferon-triggered human anti-mycobacterial responses.  a1448-530 v3393 a<p>Type I interferons (IFN-α and IFN-β) are important for protection against many viral infections, whereas type II interferon (IFN-γ) is essential for host defense against some bacterial and parasitic pathogens. Study of IFN responses in human leprosy revealed an inverse correlation between IFN-β and IFN-γ gene expression programs. IFN-γ and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in self-healing tuberculoid lesions and mediated antimicrobial activity against the pathogen Mycobacterium leprae in vitro. In contrast, IFN-β and its downstream genes, including interleukin-10 (IL-10), were induced in monocytes by M. leprae in vitro and preferentially expressed in disseminated and progressive lepromatous lesions. The IFN-γ-induced macrophage vitamin D-dependent antimicrobial peptide response was inhibited by IFN-β and by IL-10, suggesting that the differential production of IFNs contributes to protection versus pathogenesis in some human bacterial infections.</p>  a1095-9203