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...

Full description

Bibliographic Details
Main Authors: Saikat eMajumder, Amrita eBhattacharjee, Bidisha epaulchowdhury, Suchandra eBhattacharyya Majumdar, Subrata eMajumdar
Format: Article
Language:English
Published: Frontiers Media S.A. 2014-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00261/full
_version_ 1811254655794020352
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.
first_indexed 2024-04-12T17:10:54Z
format Article
id doaj.art-21a21b76034344c4b02da2cc1482f7a5
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-12T17:10:54Z
publishDate 2014-06-01
publisher Frontiers Media S.A.
record_format Article
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
work_keys_str_mv AT saikatemajumder antigenpulsedcpgodnactivateddendriticcellsinducehostprotectiveimmuneresponsebyregulatingthetregulatorycellfunctioninginleishmaniadonovaniinfectedmicecriticalroleofcxcl10
AT amritaebhattacharjee antigenpulsedcpgodnactivateddendriticcellsinducehostprotectiveimmuneresponsebyregulatingthetregulatorycellfunctioninginleishmaniadonovaniinfectedmicecriticalroleofcxcl10
AT bidishaepaulchowdhury antigenpulsedcpgodnactivateddendriticcellsinducehostprotectiveimmuneresponsebyregulatingthetregulatorycellfunctioninginleishmaniadonovaniinfectedmicecriticalroleofcxcl10
AT suchandraebhattacharyyamajumdar antigenpulsedcpgodnactivateddendriticcellsinducehostprotectiveimmuneresponsebyregulatingthetregulatorycellfunctioninginleishmaniadonovaniinfectedmicecriticalroleofcxcl10
AT subrataemajumdar antigenpulsedcpgodnactivateddendriticcellsinducehostprotectiveimmuneresponsebyregulatingthetregulatorycellfunctioninginleishmaniadonovaniinfectedmicecriticalroleofcxcl10