Co-factor-independent phosphoglycerate mutase of Leishmania donovani modulates macrophage signalling and promotes T-cell repertoires bearing epitopes for both MHC-I and MHC-II
| Autor: | Pushkar Shivam, Sarita Kumari, Shubhankar K. Singh, K K Sinha, V. N. R. Das, Fauzia Jamal, Krishna Pandey, Manas Ranjan Dikhit, Ghufran Ahmed, Manish K Singh, Pushpanjali, Amit K Dubey, Pradeep Das, Shyam Narayan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
T cell Genes MHC Class II Interleukin-1beta Coenzymes Epitopes T-Lymphocyte Genes MHC Class I Nitric Oxide Synthase Type II Lymphocyte proliferation Lymphocyte Activation Nitric Oxide Major histocompatibility complex Epitope Cell Line 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Antigen MHC class I medicine Humans Computer Simulation Phosphoglycerate Mutase biology Macrophages NF-kappa B p50 Subunit Th1 Cells Molecular biology Recombinant Proteins 030104 developmental biology Infectious Diseases medicine.anatomical_structure 030220 oncology & carcinogenesis Leukocytes Mononuclear biology.protein Cytokines Leishmaniasis Visceral Animal Science and Zoology Parasitology CD8 Leishmania donovani |
| Zdroj: | Parasitology. 145:292-306 |
| ISSN: | 1469-8161 0031-1820 |
| DOI: | 10.1017/s0031182017001494 |
| Popis: | SUMMARYImmunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β. This immune polarization was also evidenced by upregulation of nuclear factor-κ light-chain enhancer of activated B cells p50 and regulated expression of suppressor of mother against decapentaplegic protein-4. rLd-iPGAM stimulation also promoted lymphocyte proliferation and boosted the leishmaniacidal activity of macrophages by upregulating reactive oxygen species. It also induced 1·8-fold higher release of nitric oxide (NO) by promoting the transcription of inducible nitric oxide synthase gene. Besides, in silico analysis suggested the presence of major histocompatibility complex class I and II restricted epitopes, which can proficiently trigger CD8+ and CD4+ cells, respectively. This study reports rLd-iPGAM as an effective immunoprophylactic agent, which can be used in future vaccine design. |
| Databáze: | OpenAIRE |
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