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 |
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| Affiliation: | 1. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, 30130-100 Belo Horizonte, Minas Gerais, Brazil;2. Instituto de Ciências Biológicas e da Saúde, Pontifícia Universidade Católica de Minas Gerais, 30535-901 Belo Horizonte, Minas Gerais, Brazil;3. Minasfungi do Brasil Ltda, Belo Horizonte, Minas Gerais, Brazil;4. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;5. Departamento de Química Orgânica e Inorgânica, Centro de Ciências, Universidade Federal do Ceará, 60356-682 Fortaleza, Ceará, Brazil;6. Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;7. Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain;8. Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;1. JH-Institute of Molecular Medicine, Jamia Hamdard, New Delhi 110062, India;2. Department of Bio & Nano Technology, Bio & Nano Technology Centre, Guru Jambheshwar University of Science and Technology, Hisar 125001, India;3. School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India;4. BD Biosciences, Jamia Hamdard, New Delhi 110062, India;5. Division of Emerging and Transfusion Transmitted Diseases (CBER), Food and Drug Administration, Silver Spring, MD 20993, USA;6. National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India |
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| 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. |
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| Keywords: | Protein disulfide isomerase (PDI) DNA vaccine Interleukin (IL)-17A Nitric oxide Mitogen-activated protein kinase (MAPK) Visceral leishmaniasis Interferon gamma |
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