Antigen-pulsed CpG-ODN-activated dendrtic cells induce host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice: critical role of CXCL10

作者：Majumder Saikat; Bhattacharjee Amrita; Chowdhury Bidisha Paul; Majumdar Suchandra Bhattacharyya; Majumdar Subrata

来源：Frontiers in Immunology, 2014, 5: 1-9.

DOI：10.3389/fimmu.2014.00261

• Leishmania
• T regulatory cells
• vaccine
• dendritic cell
• 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 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 DC vaccination is sufficient in rendering complete protection against L. donovani infection. In probing the possible mechanism, we observe that SLA CpG DCs vaccination results in the significant decrease in Foxp3(+)GITR(+)PCTLA4(+)CD4(+)CD25(+) regulatory T cells (Treg) cell population in Leishmania-infected mice. Vaccination with these antigen-stimulated dendritic cells results in the decrease in the secretion of TGF-beta by these Treg cells by possible regulation of the SMAD signaling. Moreover, we demonstrate that a CXC chemokine, IFN-gamma-inducible protein 10 (IP-10; CXCL10), has a direct role in the regulation of CD4(+)CD25(+) Treg cells in SLA CpG DC-vaccinated parasitized mice as Treg cells isolated from IP-10-depleted vaccinated mice showed significantly increased TGF-beta production and suppressive activity.

• 出版日期2014-6-4
• 单位常州工学院