01912nas a2200241   4500000000100000008004100001653000900042653001100051653001100062653001400073653001200087653001200099100001200111700001300123700001200136700001100148700001000159700001600169700001300185700001200198245008600210520137400296       2013                            d10ap30010aNF-κB10aManLAM10aM. leprae10aleprosy10aDC SIGN1 aKumar S1 aNaqvi RA1 aBhat AA1 aRani R1 aAli R1 aAgnihotri A1 aKhanna N1 aRao D N00aIL-10 production from dendritic cells is associated with DC SIGN in human leprosy3 aThe defective antigen presenting ability of antigen presenting cells (APCs) modulates host cytokines and co-stimulatory signals that may lead to severity of leprosy. In the present study, we sought to evaluate the phenotypic features of APCs along with whether DC SIGN (DC-specific intercellular adhesion molecule-grabbing nonintegrin) influences IL-10 production while moving from tuberculoid (BT/TT) to lepromatous (BL/LL) pole in leprosy pathogenesis. The study revealed an increased expression of DC SIGN on CD11c+ cells from BL/LL patients and an impaired form of CD83 (∼50 kDa). However, the cells after treatment with GM-CSF + IL-4 + ManLAM showed an increased expression of similar form of CD83 on DCs. Upon treatment with ManLAM, DCs were found to show increased nuclear presence of NF-κB, thus leading to higher IL-10 production. High IL-10 production from ManLAM treated PBMCs further suggested the role of DC SIGN in subverting the DCs function towards BL/LL pole of leprosy. Anti-DC SIGN treatment resulting in restricted nuclear ingression of NF-κB as well as its acetylation along with enhanced T cell proliferation validated our findings. In conclusion, M. leprae component triggers DC SIGN on DCs to induce production of IL-10 by modulating intracellular signalling pathway at the level of transcription factor NF-κB towards BL/LL pole of disease.