immunomodulation in human dendritic cells leads to induction of interferon-gamma production by leishmania donovani derived kmp-11 antigen via activation of nf-κb in indian kala-azar patients
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2014
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Abstract
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-κB) 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-κB 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.
| Reference Key |
chaudhary2014biomedimmunomodulation
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| Authors | ;Rajesh Chaudhary;Ajay Amit;Anupam Yadav;Anurag Singh;Vikash Kumar;S. K. Singh;Shyam Narayan;Vidyanand Rabidas;K. Pandey;Anil Kumar;Pradeep Das;Sanjiva Bimal |
| Journal | spectrochimica acta - part a: molecular and biomolecular spectroscopy |
| Year | 2014 |
| DOI |
10.1155/2014/947606
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| URL | |
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