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 language | English (US) |
|---|---|
| Pages (from-to) | 1488-1496 |
| Number of pages | 9 |
| Journal | Immunobiology |
| Volume | 218 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2013 |
Bibliographical note
Funding Information:Authors are grateful for the immense support of Ms. Susuma, Department of Biochemistry, AIIMS, New Delhi and Ms. Ragini throughout the work. We are also thankful to CSIR and ICMR , New Delhi, India, for providing financial assistance for this study.
Keywords
- DC SIGN
- Leprosy
- ManLAM
- Mycobacterium leprae
- NF-κB
- P300
