Antigen pulsed CpG-ODN activated dendritic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10
Visceral leishmaniasis (VL), caused by Leishmania donovani, is a systemic infection of reticulo-endothelial system. There is currently no protective vaccine against VL and chemotherapy is increasingly limited due to appearance of drug resistance to first line drugs such as antimonials and amphoteric...
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Frontiers Media S.A.
2014-06-01
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Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00261/full |
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author | Saikat eMajumder Amrita eBhattacharjee Bidisha epaulchowdhury Suchandra eBhattacharyya Majumdar Subrata eMajumdar |
author_facet | Saikat eMajumder Amrita eBhattacharjee Bidisha epaulchowdhury Suchandra eBhattacharyya Majumdar Subrata eMajumdar |
author_sort | Saikat eMajumder |
collection | DOAJ |
description | Visceral leishmaniasis (VL), caused by Leishmania donovani, is a systemic infection of reticulo-endothelial system. There is currently no protective vaccine against VL and chemotherapy is increasingly limited due to appearance of drug resistance to first line drugs such as antimonials and amphotericin B. In the present study, by using a murine model of leishmaniasis we evaluated the function played by soluble leishmanial antigen (SLA) pulsed-CpG-ODN stimulated dendritic cells (SLA-CpG-DCs) in restricting the intracellular parasitic growth. We establish that a single dose of SLA-CpG-DCs vaccination is sufficient in rendering complete protection against Leishmania donovani infection. In probing the possible mechanism, we observed that SLA-CpG-DCs vaccination results in the significant decrease in Foxp3+GITR+CTLA4+CD4+CD25+ Treg cell population in Leishmania-infected mice. Vaccination with these antigen stimulated dendritic cells results in the decrease in the secretion of TGF-β by these Treg cells by possible regulation of the SMAD signalling. Moreover, we demonstrated that a CXC chemokine, IFN-γ-inducible protein 10 (IP-10), has a direct role in the regulation of CD4+CD25+ Treg cells in SLA-CpG-DCs vaccinated parasitized mice as Treg cells isolated from IP-10 depleted vaccinated mice showed significantly increased TGF-β production and suppressive activity. |
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id | doaj.art-21a21b76034344c4b02da2cc1482f7a5 |
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issn | 1664-3224 |
language | English |
last_indexed | 2024-04-12T17:10:54Z |
publishDate | 2014-06-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Immunology |
spelling | doaj.art-21a21b76034344c4b02da2cc1482f7a52022-12-22T03:23:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-06-01510.3389/fimmu.2014.0026180173Antigen pulsed CpG-ODN activated dendritic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10Saikat eMajumder0Amrita eBhattacharjee1Bidisha epaulchowdhury2Suchandra eBhattacharyya Majumdar3Subrata eMajumdar4Bose InstituteBose InstituteBose InstituteBose InstituteBose InstituteVisceral leishmaniasis (VL), caused by Leishmania donovani, is a systemic infection of reticulo-endothelial system. There is currently no protective vaccine against VL and chemotherapy is increasingly limited due to appearance of drug resistance to first line drugs such as antimonials and amphotericin B. In the present study, by using a murine model of leishmaniasis we evaluated the function played by soluble leishmanial antigen (SLA) pulsed-CpG-ODN stimulated dendritic cells (SLA-CpG-DCs) in restricting the intracellular parasitic growth. We establish that a single dose of SLA-CpG-DCs vaccination is sufficient in rendering complete protection against Leishmania donovani infection. In probing the possible mechanism, we observed that SLA-CpG-DCs vaccination results in the significant decrease in Foxp3+GITR+CTLA4+CD4+CD25+ Treg cell population in Leishmania-infected mice. Vaccination with these antigen stimulated dendritic cells results in the decrease in the secretion of TGF-β by these Treg cells by possible regulation of the SMAD signalling. Moreover, we demonstrated that a CXC chemokine, IFN-γ-inducible protein 10 (IP-10), has a direct role in the regulation of CD4+CD25+ Treg cells in SLA-CpG-DCs vaccinated parasitized mice as Treg cells isolated from IP-10 depleted vaccinated mice showed significantly increased TGF-β production and suppressive activity.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00261/fullLeishmaniadendritic cellVaccineT regulatory cellsCXCL10 |
spellingShingle | Saikat eMajumder Amrita eBhattacharjee Bidisha epaulchowdhury Suchandra eBhattacharyya Majumdar Subrata eMajumdar Antigen pulsed CpG-ODN activated dendritic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10 Frontiers in Immunology Leishmania dendritic cell Vaccine T regulatory cells CXCL10 |
title | Antigen pulsed CpG-ODN activated dendritic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10 |
title_full | Antigen pulsed CpG-ODN activated dendritic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10 |
title_fullStr | Antigen pulsed CpG-ODN activated dendritic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10 |
title_full_unstemmed | Antigen pulsed CpG-ODN activated dendritic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10 |
title_short | Antigen pulsed CpG-ODN activated dendritic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10 |
title_sort | antigen pulsed cpg odn activated dendritic cells induce host protective immune response by regulating the t regulatory cell functioning in leishmania donovani infected mice critical role of cxcl10 |
topic | Leishmania dendritic cell Vaccine T regulatory cells CXCL10 |
url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00261/full |
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