Leishmania Major Large RAB GTPase is Highly Immunogenic in Individuals Immune to Cutaneous and Visceral Leishmaniasis

Overview

Journal Parasit Vectors

Publisher Biomed Central

Specialties Parasitology
Tropical Medicine

Date 2017 Apr 19

PMID 28416006

Citations 5

Authors

Rym Chamakh-Ayari

Mehdi Chenik

Ahmed Sahbi Chakroun

Narges Bahi-Jaber

Karim Aoun

Amel Meddeb-Garnaoui

Affiliations

Soon will be listed here.

Abstract

Background: We previously identified a Leishmania (L.) major large RAB GTPase (LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania species while displaying low level of homology with mammalian homologues. Leishmania small RAB GTPases proteins have been involved in regulation of exocytic and endocytic pathways whereas the role of large RAB GTPases proteins has not been characterized yet. We report here the immunogenicity of both recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L. major or L. infantum.

Methods: PBMC were isolated from individuals cured of L. major (CCLm) or from healthy individuals. The latter were subdivided into high or low IFN-γ responders. Healthy high IFN-γ responders, considered as asymptomatics, were living in an endemic area for L. major (HHRLm) or L. infantum (HHRLi). Healthy low IFN-γ responders (HLR) were considered as naïve controls. Cells from all volunteers were stimulated with rLmlRAB or rLmlRABC. Cytokines were analysed by CBA and ELISA and phenotypes of IFN-γ-producing cells were analysed by flow cytometry.

Results: Both rLmlRAB and rLmlRABC induced high significant levels of IFN-γ in CCLm, HHRLm and HHRLi groups. Phenotype analysis of rLmlRAB and rLmlRABC-stimulated T cells in CCLm individuals showed a significant increase in the percentage of specific IFN-γ-producing CD4+ and CD8+ T cells. rLmlRAB induced significant granzyme B levels in CCLm and HHRLm. Low but significant granzyme B levels were detected in naïve group. IL-10 was detected in immune and naïve individuals.

Conclusion: We showed that rLmlRAB protein and its divergent carboxy-terminal part induced a predominant Th1 response in individuals immune to L. major or L. infantum. Our results suggest that rLmlRAB and rLmlRABC proteins are potential cross-species vaccine candidates against cutaneous and visceral leishmaniasis.

Citing Articles

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PMID: 36983046 PMC: 10054446. DOI: 10.3390/ijms24065972.

Cutaneous Leishmaniasis in Algeria; Highlight on the Focus of M'Sila.

Beniklef R, Aoun K, Boudrissa K, Abid M, Cherif K, Aissi W Microorganisms. 2021; 9(5).

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Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines.

Andrade J, Goncalves L, Liarte D, Lima D, Guimaraes F, Resende D Parasit Vectors. 2020; 13(1):600.

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Design of multi-epitope peptides containing HLA class-I and class-II-restricted epitopes derived from immunogenic Leishmania proteins, and evaluation of CD4+ and CD8+ T cell responses induced in cured cutaneous leishmaniasis subjects.

Hamrouni S, Bras-Goncalves R, Kidar A, Aoun K, Chamakh-Ayari R, Petitdidier E PLoS Negl Trop Dis. 2020; 14(3):e0008093.

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Attenuated Induce a High Level of Protection against in BALB/c Mice.

Noorpisheh Ghadimi S, Homayoon L, Shahriarirad R, Fatehpour S, Rastegarian M, Sarkari B Iran J Parasitol. 2019; 14(2):310-317.

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