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

Rabiaa Manel Sghaier; Imen Aissa; Hanene Attia; Aymen Bali; Pablo A. Leon Martinez; Ghada Mkannez; Fatma Zahra Guerfali; Youssef Gargouri; Dhafer Laouini

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

Rabiaa Manel Sghaier ^{1, 2} Imen Aissa ³ Hanene Attia ^{1, 2} Aymen Bali ^{1, 2} Pablo A. Leon Martinez ^{1, 2} Ghada Mkannez ^{1, 2} Fatma Zahra Guerfali ^{1, 2} Youssef Gargouri ³ Dhafer Laouini ^{1, 2, *}

* Corresponding author

1 LR11IPT02 - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection

2 UTM - Université Tunis El Manar

3 ENIS - École Nationale d'Ingénieurs de Sfax | National School of Engineers of Sfax

Abstract : 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 major anti-leishmanial activity lipophilic tyrosyl ester parasite load

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Microbiology and Parasitology

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https://hal-riip.archives-ouvertes.fr/pasteur-01441787
Contributor : Institut Pasteur Tunis <>
Submitted on : Friday, January 20, 2017 - 10:59:50 AM
Last modification on : Tuesday, July 23, 2019 - 11:32:03 AM

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

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

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