Leishmania donovani: impairment of the cellular immune response against recombinant ornithine decarboxylase protein as a possible evasion strategy of Leishmania in visceral leishmaniasis

Yadav, Anupam; Amit, Ajay; Chaudhary, Rajesh; Chandel, Arvind K. Singh; Mahantesh, Vijay; Suman, Shashi S.; Singh, Subhankar K.; Dikhit, Manas Ranjan; Ali, Vahab; Rabidas, Vidyanand; Pandey, Krishna; Kumar, Anil; Das, Pradeep; Bimal, Sanjiva

doi:10.1016/j.ijpara.2014.08.013

Cited by 23 publications

(21 citation statements)

References 45 publications

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“…The PBMCs (1×10 6 /mL) were cultured in 6‐well plates for overnight incubation at 5% CO 2 with one of the individual peptides (P1 and P3). Stimulation with SLA was run in parallel to all experiments as described previously . After overnight incubation followed by 4 hours incubation with the protein transport inhibitor brefeldin A (1 μg/mL), the cells were pelleted, washed with phosphate‐buffered saline and stained with anti‐CD3‐PerCP conjugated antibodies (BD Biosciences) and anti‐CD8‐FITC (BD Biosciences) for 30 minutes at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…Various strategies have been employed to date to develop specific antileishmanial vaccines such as killed parasites, live attenuated parasites, subunit vaccines using proteins of different stages of the parasite life cycle and DNA vaccines, dendritic cell‐based vaccines and salivary antigen‐based vaccines . Many of these strategies have resulted in protection of the mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Vaccine potential of HLA‐A2 epitopes from Leishmania Cysteine Protease Type III (CPC)

Dikhit

Amit

Singh

et al. 2017

Parasite Immunology

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Although the precise host-defence mechanisms are not completely understood, T-cell-mediated immune responses are believed to play a pivotal role in controlling parasite infection. In this study, the potential HLA*A2 restricted peptides were predicted and the ability of peptides to bind HLA-A*02 was confirmed by a MHC stabilization assay. Two of the peptides tested stabilized HLA-A*02: (a) LLATTVSGL (P1) and (b) LMTNGPLEV (P3). The potential of the peptides to generate protective immune response was evaluated in patients with treated visceral leishmaniasis as well as in healthy control subjects. Our data suggest that CD8 T-cell proliferation against the selected peptide was significantly higher compared to unstimulated culture conditions. The stimulation of peripheral blood mononuclear cells with epitopes individually or as a cocktail upregulated IFN-γ production, which indicates its pivotal role in protective immune response. The IFN-γ production was mainly in a CD8 T-cells-dependent manner, which suggested that these epitopes had an immunoprophylactic potential in a MHC class I-dependent manner. Moreover, no role of the CD3 T cell was observed in the IL-10 production against the selected peptides, and no role was found in disease pathogenesis. Further studies on the role of these synthetic peptides may contribute significantly to developing a polytope vaccine idea towards leishmaniasis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vaccine potential of HLA‐A2 epitopes from Leishmania Cysteine Protease Type III (CPC)

Dikhit

Amit

Singh

et al. 2017

Parasite Immunology

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“…[10][11][12][13] However, none of these strategies offer significant protection and are yet to be applied in phase I clinical trial. Our previous studies revealed that ornithine decarboxylase (ODC) derived from Leishmania donovani have the potential to elicit the immune cells by influencing multifunctional CD4 + and CD8 + T cell-mediated activities 14,15 with a robust Th1 immune response and reduced parasite load in spleens. 14 Simultaneous up-regulated IL-10 against this target antigen is thought to plunge their vaccine potential.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Evaluating the immunomodulatory responses of LdODC‐derived MHC Class‐II restricted peptides against VL

Pandey

Dikhit

Kumar

et al. 2020

Parasite Immunology

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In a bid to develop a novel immunoprophylactic measure against visceral leishmaniasis (VL), MHC class‐II–restricted epitopes of LdODC were identified by reverse vaccinology approach. Five consensus HLA‐DRB1*0101‐restricted epitopes were screened. The analysis revealed that the set of epitopes was presented by at least 54 diverse MHC class‐II alleles. Based on in silico screening, followed by molecular dynamics simulation, population coverage analysis, and HLA cross‐presentation ability, five best epitopes were evaluated. PBMCs isolated from treated VL subjects, when stimulated with synthetic peptide alone or as a cocktail of peptides, triggered a secretory IFN‐γ, but not the IL‐10 level. Support in this notion came from intracellular cytokine level with a considerable up‐regulated IFN‐γ produced by CD4+ T cells. Also, the enhanced IFN‐γ seemed to be augmented with the activation of macrophages with prominent IL‐12 production. Therefore, it can be concluded that the screened MHC class‐II–restricted epitope hotspots derived from Leishmania ODC can trigger CD4+ T cells, which can skew macrophage functions towards protection. However, a detailed analysis can explore its potentiality as a vaccine candidate.

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“…Furthermore, it was found that ethanolic extract of leaves from B. fagaroides inhibits 50 % of the activity of ornithine decarboxylase (ODC) at a concentration of 8 mg/mL (Rosas-Arreguin et al, 2008). ODC catalyzes the decarboxylation of ornithine to produce putrescine and is essential for biosynthesis, polyamines and trypanothione of parasitic protozoa and may be a potential target for the development of new drugs against Leishmania (Yadav et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

In Vivo and in Vitro Antileishmanial Effects of Methanolic Extract From Bark of Bursera Aptera

Oj¹,

Aa²,

Pa³

et al. 2017

Afr J Tradit Complement Altern Med

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Background: Cutaneous leishmaniasis lacks effective and well-tolerated treatments. The current therapies mainly rely on antimonial drugs that are inadequate because of their poor efficacy. Traditional medicine offers a complementary alternative for the treatment of various diseases. Additionally, several plants have shown success as anti-leishmanial agents. Therefore, we sought to evaluate the in vitro and in vivo activity of MEBA against Leishmania mexicana . Materials and Methods: Methanolic extract of B. aptera was obtained by macetration, after we determined in vitro anti-leishmanial activity of MEBA by MTT assay and the induced apoptosis in promastigotes by flow cytometry. To analyze the in vivo anti-leishmanial activity, we used infected mice that were treated and not treated with MEBA and we determined the levels of cytokines using ELISA. The phytochemical properties were determined by CG-MS and DPPH assay. Results: We determined of LC 50 of 0.408 mg/mL of MEBA for in vitro anti-leishmanial activity. MEBA induced apoptosis in promastigotes (15.3% ± 0.86). Treated mice exhibited smaller lesions and contained significantly fewer parasites than did untreated mice; in addition, we found that IFN-γ and TNF-α increased in the sera of MEBA-treated mice. GC-MS analysis showed that podophyllotoxin was the most abundant compound. Evaluation of the activity by DPPH assay demonstrated an SC 50 of 11.72 μg/mL. Conclusion: Based on the above data, it was concluded that MEBA is a good candidate in the search for new anti-leishmanial agents.

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Leishmania donovani: impairment of the cellular immune response against recombinant ornithine decarboxylase protein as a possible evasion strategy of Leishmania in visceral leishmaniasis

Cited by 23 publications

References 45 publications

Vaccine potential of HLA‐A2 epitopes from Leishmania Cysteine Protease Type III (CPC)

Vaccine potential of HLA‐A2 epitopes from Leishmania Cysteine Protease Type III (CPC)

Retracted: Evaluating the immunomodulatory responses of LdODC‐derived MHC Class‐II restricted peptides against VL

In Vivo and in Vitro Antileishmanial Effects of Methanolic Extract From Bark of Bursera Aptera

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