IL-10 production from dendritic cells is associated with DC SIGN in human leprosy

Sudhir Kumar, Raza Ali Naqvi, Ajaz A. Bhat, Richa Rani, Riyasat Ali, Abhishek Agnihotri, Neena Khanna, D. N. Rao

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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 (~50kDa). 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.

Original languageEnglish (US)
Pages (from-to)1488-1496
Number of pages9
JournalImmunobiology
Volume218
Issue number12
DOIs
StatePublished - Dec 1 2013

Keywords

  • DC SIGN
  • Leprosy
  • ManLAM
  • Mycobacterium leprae
  • NF-κB
  • P300

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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    Kumar, S., Naqvi, R. A., Bhat, A. A., Rani, R., Ali, R., Agnihotri, A., Khanna, N., & Rao, D. N. (2013). IL-10 production from dendritic cells is associated with DC SIGN in human leprosy. Immunobiology, 218(12), 1488-1496. https://doi.org/10.1016/j.imbio.2013.05.004