Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice

• DOI: 10.1016/j.molimm.2016.12.022
• Publication Date: 2017-01-06T04:25:13Z
• Authors: Ajay Amit; Vijayamahantesh; Manas R. Dikhit; Ashish Kumar Singh; Vikash Kumar; Shashi S. Suman; Ashu Singh; Akhilesh Kumar; Ajit Kumar Thakur; Vidyanand Ravi Das; Pradeep Das; Sanjiva Bimal
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; Blotting, Western; Protein Disulfide-Isomerases; Protozoan Proteins; Enzyme-Linked Immunosorbent Assay; Th1 Cells; Flow Cytometry; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Vaccines, DNA; Animals; Leishmaniasis, Visceral; Th17 Cells; Leishmaniasis Vaccines; Leishmania donovani; Signal Transduction

In the present study, the efficacy of Leishmania donovani protein disulfide isomerase (LdPDI) as a DNA vaccine was evaluated in BALB/C mice. Mice immunized with the LdPDI-DNA construct were found to be the most immuno-reactive, as the construct induced higher T-cell proliferation. The increased T-cell proliferation was associated with a substantial rise in Th1 and Th17+ CD4 cell response and triggered a higher proportion of CD8+ T cells for the release of interferon-gamma along with a reduced splenic parasite load on Days20 and 60 post challenge (PC). Furthermore, the vaccine construct triggered increased interferon (IFN)-γ, interleukin(IL)-17A, and IL-22 release accompanied by decreased extracellular signal-regulated kinases (ERK) 1/2 signaling and increased mitogen-activated protein kinase (MAPK) signaling coinciding with an increase in the amount of nitrite and reactive oxygen species (ROS)in vaccinating the splenocyts. We summarize from our data that the PDI-DNA construct of Leishmania donovani has the potential to elicit protective immunity through the pro-inflammatory cytokines of CD8+ and CD4+(Th1 and Th17) following an intervention in the downstream signaling event of ERK1/2 (probably through p38MAPK signaling). Therefore, the study suggests a new control against visceral leishmaniasis in the future.