IL-10 production from dendritic cells is associated with DC SIGN in human leprosy.
The 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, Mycobacterium 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.
['Kumar|Sudhir|S|', 'Naqvi|Raza Ali|RA|', 'Bhat|Ajaz A|AA|', 'Rani|Richa|R|', 'Ali|Riyasat|R|', 'Agnihotri|Abhishek|A|', 'Khanna|Neena|N|', 'Rao|D N|DN|']
D000107:Acetylation D000293:Adolescent D000328:Adult D019138:Antibodies, Blocking D015703:Antigens, CD D015815:Cell Adhesion Molecules D049109:Cell Proliferation D002478:Cells, Cultured D003713:Dendritic Cells D018450:Disease Progression D005260:Female D016178:Granulocyte-Macrophage Colony-Stimulating Factor D006801:Humans D057131:Immune Evasion D016753:Interleukin-10 D015847:Interleukin-4 D037181:Lectins, C-Type D007918:Leprosy D008070:Lipopolysaccharides D008297:Male D008875:Middle Aged D009166:Mycobacterium leprae D016328:NF-kappa B D011956:Receptors, Cell Surface D013601:T-Lymphocytes D055815:Young Adult
DC SIGN Leprosy ManLAM NF-κB Mycobacterium leprae p300