Evaluation of Leishmania donovani disulfide isomerase as a potential target of cellular immunity against visceral leishmaniasis.

Abstract

In Leishmania species, protein disulfide isomerase (PDI) - a redox chaperone is primarily associated with virulence and survival. The precise mechanism, especially in relation to redox changes and its effects on immunological responses in visceral leishmaniasis (VL) is not completely understood as yet. Therefore, we purified a recombinant PDI from Leishmania donovani (r-LdPDI) which was of ∼15 kDa molecular size and examined its effects on immunological responses in peripheral blood (PBMC) of human VL cases. For these studies, alanine was tested as an inhibitor and was used in parallel to all experiments. This protein was identified to have a direct correlation with parasite growth which significantly increased number of promastigotes as well as axenic amastigotes after 96 h of culture. Our experiments examining the immunological response against r-LdPDI also indicate the activation of pro-L. donovani dictated immunological responses in VL. The stimulation of PBMC with r-LdPDI induced lactate dehydrogenase (LDH) activities and up regulated interleukin-10 (IL-10) production but not the HLA-DR expression, Nitric oxide (NO) release and IFN-γ production indicating a pivoted role for r-LdPDI in causing a strong immunosuppression in a susceptible host. Further, we observed that an addition of alanine in L. donovani culture offers a significant inhibition in growth of parasite and helps in reconstitution of protective immune response in VL cases. Therefore, we demonstrate a future cross talk on use of alanine which can reduce the activities of PDI of L. donovani, eliminating the parasite induced immunosuppression and inducing collateral host protective response in VL.

• Authors: Ajay Amit, Rajesh Chaudhary, Anupam Yadav, Shashi S Suman, Shyam Narayan, V N R Das, K Pandey, S K Singh, Bipin K Singh, Vahab Ali, Pradeep Das, Sanjiva Bimal
• Journal: Cellular immunology (Cell Immunol) 2014 May-Jun Vol. 289 Issue 1-2 Pg. 76-85 ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 24732062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• IL10 protein, human
• Immunologic Factors
• Interleukin-10
• Nitric Oxide
• Interferon-gamma
• L-Lactate Dehydrogenase
• Protein Disulfide-Isomerases
• Alanine

Topics

• Adolescent
• Adult
• Alanine (pharmacology)
• Female
• Humans
• Immunity, Cellular (immunology)
• Immunologic Factors (immunology)
• Immunosuppression Therapy
• Interferon-gamma (biosynthesis)
• Interleukin-10 (biosynthesis)
• L-Lactate Dehydrogenase
• Leishmania donovani (enzymology)
• Leishmaniasis, Visceral (immunology)
• Macrophages (immunology, parasitology)
• Male
• Nitric Oxide (metabolism)
• Protein Disulfide-Isomerases (immunology)
• Young Adult