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Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice

Published online by Cambridge University Press:  17 June 2016

RABIAA M. SGHAIER ,
IMEN AISSA ,
HANÈNE ATTIA ,
AYMEN BALI ,
PABLO A. LEON MARTINEZ ,
GHADA MKANNEZ ,
FATMA Z. GUERFALI ,
YOUSSEF GARGOURI  and
DHAFER LAOUINI
RABIAA M. SGHAIER
Affiliation:
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia Université Tunis El Manar, Tunis, 1068, Tunisia
IMEN AISSA
Affiliation:
Laboratoire de Biochimie et de Génie Enzymatique des Lipases, Ecole Nationale d'Ingénieurs de Sfax (ENIS), Université de Sfax, Route de Soukra, BP 1173, 3038 Sfax, Tunisie
HANÈNE ATTIA
Affiliation:
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia Université Tunis El Manar, Tunis, 1068, Tunisia
AYMEN BALI
Affiliation:
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia Université Tunis El Manar, Tunis, 1068, Tunisia
PABLO A. LEON MARTINEZ
Affiliation:
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia Université Tunis El Manar, Tunis, 1068, Tunisia
GHADA MKANNEZ
Affiliation:
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia Université Tunis El Manar, Tunis, 1068, Tunisia
FATMA Z. GUERFALI
Affiliation:
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia Université Tunis El Manar, Tunis, 1068, Tunisia
YOUSSEF GARGOURI
Affiliation:
Laboratoire de Biochimie et de Génie Enzymatique des Lipases, Ecole Nationale d'Ingénieurs de Sfax (ENIS), Université de Sfax, Route de Soukra, BP 1173, 3038 Sfax, Tunisie
DHAFER LAOUINI*
Affiliation:
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia Université Tunis El Manar, Tunis, 1068, Tunisia
*
*Corresponding author: Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, LR11IPT02, Tunis-Belvédère, 1002, Tunisia and Université Tunis El Manar, Tunis, 1068, Tunisia. Tel.: +216 71 845 415. E-mail: dhafer_l@yahoo.ca
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Summary

Synthesized lipophilic tyrosyl ester derivatives with increasing lipophilicity were effective against Leishmania (L.) major and Leishmania infantum species in vitro. These findings prompted us to test in vivo leishmanicidal properties of these molecules and their potential effect on the modulation of immune responses. The experimental BALB/c model of cutaneous leishmaniasis was used in this study. Mice were infected with L. major parasites and treated with three in vitro active tyrosyl esters derivatives.

Among these tested tyrosylcaprate (TyC) compounds, only TyC10 exhibited an in vivo anti-leishmanial activity, when injected sub-cutaneously (s.c.). TyC10 treatment of L. major-infected BALB/c mice resulted in a decrease of lesion development and parasite load. TyC10 s.c. treatment of non-infected mice induced an imbalance in interferon γ/interleukin 4 (IFN-γ/IL-4) ratio cytokines towards a Th1 response. Our results indicate that TyC10 s.c. treatment improves lesions’ healing and parasite clearance and may act on the cytokine balance towards a Th1 protective response by decreasing IL-4 and increasing IFN-γ transcripts. TyC10 is worthy of further investigation to uncover its mechanism of action that could lead to consider this molecule as a potential drug candidate.

Keywords

Leishmania majorlipophilic tyrosyl esteranti-leishmanial activityparasite load
Type
Research Article
Information
Parasitology , Volume 143 , Issue 12 , October 2016 , pp. 1615 - 1621
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Copyright
Copyright © Cambridge University Press 2016 

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