title: 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.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Amit
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chaudhary
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Yadav
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: Shashi S
authors.initials: SS
authors.lastname: Suman
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: Shyam
authors.initials: S
authors.lastname: Narayan
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: V N R
authors.initials: VN
authors.lastname: Das
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: K
authors.initials: K
authors.lastname: Pandey
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: Bipin K
authors.initials: BK
authors.lastname: Singh
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: Vahab
authors.initials: V
authors.lastname: Ali
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Das
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, India. Electronic address: drsbimal24@yahoo.com.
authors.forename: Sanjiva
authors.initials: S
authors.lastname: Bimal
mesh_terms: D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase; D007893:Leishmania donovani / Q000201:enzymology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000276:immunology*; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D007155:Immunologic Factors; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase; D019704:Protein Disulfide-Isomerases; D000409:Alanine
keywords: Inducible nitric oxide; Interferon-gamma; Interleukin-10; Lactate dehydrogenase; Leishmania donovani; Protein disulfide isomerase; Visceral leishmaniasis