NDLI: 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

Content Provider	PubMed Central
Author	Chaudhary, Rajesh Amit, Ajay Yadav, Anupam Singh, Anurag Kumar, Vikash Singh, S. K. Narayan, Shyam Rabidas, Vidyanand Pandey, K. Kumar, Anil Das, Pradeep Bimal, Sanjiva
Copyright Year	2014
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.
Related Links	http://dx.doi.org/10.1155/2014/947606
Starting Page	947606
File Format	PDF
ISSN	23146133
e-ISSN	23146141
Journal	BioMed Research International
Volume Number	2014
Language	English
Publisher	Hindawi Publishing Corporation
Publisher Date	2014-01-01
Access Restriction	Open
Rights Holder	Hindawi Publishing Corporation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

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