PMID- 24587999 OWN - NLM STAT- MEDLINE DCOM- 20141015 LR - 20221219 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2014 DP - 2014 TI - Immunomodulation in human dendritic cells leads to induction of interferon-gamma production by Leishmania donovani derived KMP-11 antigen via activation of NF-kappaB in Indian kala-azar patients. PG - 947606 LID - 10.1155/2014/947606 [doi] LID - 947606 AB - Dendritic cells (DCs) and macrophages (MPhis) 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 MPhis to T cells in Indian patients with VL. Patients with DCS and MPhis were directed against a purified Leishmania donovani antigen (KMP-11) and phytohaemagglutinin (PHA). The cytokines (IL-12, IL-10, and TGF-beta) producing abilities of the DCs and MPhis against these antigens were determined by flow cytometry. The transcription factor (NF-kappaB) and T-cell cytokine support (IFN-gamma, 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-beta expression in the MPhis 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 MPhis of VL patients. In contrast, the presentation of KMP-11 antigen by DCs to T-lymphocytes in VL patients significantly increased the IFN-gamma produced by these immune cells, whereas the levels of IL-10 were significantly elevated after presentation of KMP-11 antigen by MPhis. The VL patients were observed with severely dysfunctional MPhis in terms of NF-kappaB 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. FAU - Chaudhary, Rajesh AU - Chaudhary R AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Amit, Ajay AU - Amit A AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Yadav, Anupam AU - Yadav A AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Singh, Anurag AU - Singh A AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Kumar, Vikash AU - Kumar V AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Singh, S K AU - Singh SK AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Narayan, Shyam AU - Narayan S AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Rabidas, Vidyanand AU - Rabidas V AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Pandey, K AU - Pandey K AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Kumar, Anil AU - Kumar A AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Das, Pradeep AU - Das P AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. FAU - Bimal, Sanjiva AU - Bimal S AD - Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India ; Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar 800007, India. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Retracted Publication DEP - 20140122 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Membrane Glycoproteins) RN - 0 (NF-kappa B) RN - 0 (Protozoan Proteins) RN - 0 (kinetoplastid membrane protein 11, Leishmania donovani) RN - 82115-62-6 (Interferon-gamma) SB - IM RIN - Biomed Res Int. 2022 Dec 7;2022:9854346. PMID: 36531649 MH - Adolescent MH - Adult MH - Dendritic Cells/immunology/metabolism MH - Humans MH - Immunomodulation MH - Interferon-gamma/*biosynthesis/immunology MH - Leishmania donovani/immunology/metabolism/pathogenicity MH - Leishmaniasis, Visceral/*genetics/immunology/parasitology MH - Male MH - Membrane Glycoproteins/immunology/*metabolism MH - Middle Aged MH - NF-kappa B/*biosynthesis/genetics MH - Protozoan Proteins/immunology/*metabolism MH - T-Lymphocytes/immunology/metabolism PMC - PMC3919100 EDAT- 2014/03/04 06:00 MHDA- 2014/10/16 06:00 PMCR- 2014/01/22 CRDT- 2014/03/04 06:00 PHST- 2013/09/16 00:00 [received] PHST- 2013/12/12 00:00 [revised] PHST- 2013/12/17 00:00 [accepted] PHST- 2014/03/04 06:00 [entrez] PHST- 2014/03/04 06:00 [pubmed] PHST- 2014/10/16 06:00 [medline] PHST- 2014/01/22 00:00 [pmc-release] AID - 10.1155/2014/947606 [doi] PST - ppublish SO - Biomed Res Int. 2014;2014:947606. doi: 10.1155/2014/947606. Epub 2014 Jan 22.