Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice.
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.
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvédère, 1002,Tunisia.
Rabiaa M
RM
Sghaier
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.
Imen
I
Aissa
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvédère, 1002,Tunisia.
Hanène
H
Attia
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvédère, 1002,Tunisia.
Aymen
A
Bali
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvédère, 1002,Tunisia.
Pablo A
PA
Leon Martinez
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvédère, 1002,Tunisia.
Ghada
G
Mkannez
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvédère, 1002,Tunisia.
Fatma Z
FZ
Guerfali
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.
Youssef
Y
Gargouri
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvédère, 1002,Tunisia.
Dhafer
D
Laouini
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D018417:Th1 Cells / Q000276:immunology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000981:Antiprotozoal Agents; D016207:Cytokines; D007155:Immunologic Factors; D014443:Tyrosine
Leishmania major; anti-leishmanial activity; lipophilic tyrosyl ester; parasite load