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Dendritic cells (DCs) and macrophages (MΦs) 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 MΦs to T cells in Indian patients with VL. Patients with DCS and MΦs were directed against a purified  Leishmania donovani  antigen (KMP-11) and phytohaemagglutinin (PHA). The cytokines (IL-12, IL-10, and TGF- β ) producing abilities of the DCs and MΦs against these antigens were determined by flow cytometry. The transcription factor (NF- κ B) and T-cell cytokine support (IFN- γ , 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- β  expression in the MΦs 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 MΦs of VL patients. In contrast, the presentation of KMP-11 antigen by DCs to T-lymphocytes in VL patients significantly increased the IFN- γ  produced by these immune cells, whereas the levels of IL-10 were significantly elevated after presentation of KMP-11antigen by MΦs. The VL patients were observed with severely dysfunctional MΦs in terms of NF- κ 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.

biomed research international

Immunomodulation in Human Dendritic Cells Leads to Induction of Interferon-Gamma Production by<i>Leishmania donovani</i>Derived KMP-11 Antigen via Activation of NF-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>κ</mml:mi></mml:mrow></mml:math>B in Indian Kala-Azar Patients

Immunomodulation in Human Dendritic Cells Leads to Induction of Interferon-Gamma Production byLeishmania donovaniDerived KMP-11 Antigen via Activation of NF-κB in Indian Kala-Azar Patients