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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

Published online by Cambridge University Press:  15 November 2017

MANISH K. SINGH ,
FAUZIA JAMAL ,
AMIT K. DUBEY ,
PUSHKAR SHIVAM ,
SARITA KUMARI ,
PUSHPANJALI ,
GHUFRAN AHMED ,
MANAS R. DIKHIT ,
S. NARAYAN  and
V. N. R. DAS
...Show all authors
MANISH K. SINGH
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
FAUZIA JAMAL
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
AMIT K. DUBEY
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India National Institute of Pharmaceutical Education and Research, Hajipur 844102, India
PUSHKAR SHIVAM
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
SARITA KUMARI
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
PUSHPANJALI
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
GHUFRAN AHMED
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
MANAS R. DIKHIT
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
S. NARAYAN
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
V. N. R. DAS
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
KRISHNA PANDEY
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
K. K. SINHA
Affiliation:
Post Graduate Department of Botany, Tilka Manjhi Bhagalpur University, Bhagalpur, 812007, India
P. DAS
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
SHUBHANKAR K. SINGH*
Affiliation:
Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India
*
*Corresponding author: Microbiology Division, RMRIMS (ICMR), Agamkuan, Patna-800007, India. E-mail: sksrmri@yahoo.com, sksingh@icmr.org.in
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Summary

Immunoactivation 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.

Keywords

Leishmania donovanico-factor-independent phosphoglycerate mutaseinnate immunityadaptive immunityvisceral leishmaniasis
Type
Research Article
Information
Parasitology , Volume 145 , Issue 3 , March 2018 , pp. 292 - 306
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Copyright
Copyright © Cambridge University Press 2017 

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