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BioMed Research International
Volume 2014, Article ID 947606, 12 pages
http://dx.doi.org/10.1155/2014/947606
Research Article

Immunomodulation in Human Dendritic Cells Leads to Induction of Interferon-Gamma Production by Leishmania donovani Derived KMP-11 Antigen via Activation of NF- B in Indian Kala-Azar Patients

1Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India
2Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India

Received 16 September 2013; Revised 12 December 2013; Accepted 17 December 2013; Published 22 January 2014

Academic Editor: Mehdi Chenik

Copyright © 2014 Rajesh Chaudhary et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dendritic cells (DCs) and macrophages (M s) are well-known antigen presenting cells with an ability to produce IL-12 which indicates that they have potential of directing acquired immunity toward a Th1-biased response. The aim of this study was to examine the effect of Leishmania specific KMP-11 antigen through comparison of immune responses after presentation by DCs and M s to T cells in Indian patients with VL. Patients with DCS and M s were directed against a purified Leishmania donovani antigen (KMP-11) and phytohaemagglutinin (PHA). The cytokines (IL-12, IL-10, and TGF- ) producing abilities of the DCs and M s against these antigens were determined by flow cytometry. The transcription factor (NF- B) and T-cell cytokine support (IFN- , IL-10), which could be significant in effector immune function, were also determined. Severe hindrance in the immune protection due to Leishmania parasites, as revealed by decreased expression of IL-12 and upregulation of IL-10 and TGF- expression in the M s compared to DCs, occurred in VL patients. The production of IL-12 in response to L. donovani KMP-11 antigen was increased in DCs which was reduced in M s of VL patients. In contrast, the presentation of KMP-11 antigen by DCs to T-lymphocytes in VL patients significantly increased the IFN- produced by these immune cells, whereas the levels of IL-10 were significantly elevated after presentation of KMP-11antigen by M s. The VL patients were observed with severely dysfunctional M s in terms of NF- B activity that could be recovered only after stimulation of DCs with L. donovani KMP-11 antigen. Immunologically the better competitiveness of KMP-11 antigen through a dendritic cell delivery system may be used to revert T-cell anergy, and control strategy can be designed accordingly against kala-azar.