title: 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.
abstract: 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.
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Amit
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India; Dept. of Biotechnology, National Institutes of Pharmaceutical Education and Research, Hajipur 844102, India.
authors.lastname: Vijayamahantesh
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India; Dept. of Bioinformatics, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Manas R
authors.initials: MR
authors.lastname: Dikhit
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India; Dept. of Pathology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Dept. of Molecular Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Shashi S
authors.initials: SS
authors.lastname: Suman
authors.affiliation: Dept. of Biotechnology, National Institutes of Pharmaceutical Education and Research, Hajipur 844102, India.
authors.forename: Ashu
authors.initials: A
authors.lastname: Singh
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Dept. of Microbiology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Ajit Kumar
authors.initials: AK
authors.lastname: Thakur
authors.affiliation: Dept. of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Vidyanand Ravi
authors.initials: VR
authors.lastname: Das
authors.affiliation: Dept. of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Das
authors.affiliation: Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India. Electronic address: drsbimal24@yahoo.com.
authors.forename: Sanjiva
authors.initials: S
authors.lastname: Bimal
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007893:Leishmania donovani; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019704:Protein Disulfide-Isomerases / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D019704:Protein Disulfide-Isomerases
keywords: DNA vaccine; Interferon gamma; Interleukin (IL)-17A; Mitogen-activated protein kinase (MAPK); Nitric oxide; Protein disulfide isomerase (PDI); Visceral leishmaniasis