Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice
| Autor: | Fatma Z. Guerfali, Hanène Attia, Youssef Gargouri, Pablo A. Leon Martinez, Ghada Mkannez, Aymen Bali, Dhafer Laouini, Imen Aissa, Rabiaa M. Sghaier |
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| Přispěvatelé: | Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Tunis El Manar (UTM), École Nationale d'Ingénieurs de Sfax | National School of Engineers of Sfax (ENIS), This work received financial support from the Tunisian Ministry of Higher Education and Scientific Research to the Transmission, Control and Immunobiology of Infections Laboratory (LR11IPT02, D. Laouini)., We thank Mr A. Marouani and Dr Z. Ben Lasfer (Animal Facilities of the Institut Pasteur de Tunis) for their help conducting this study. We are also grateful to Ms S. Amouri for her help and thankful to Dr K. Ben-Aissa (Washignton, USA) and Dr S. Gritli (Department of Oto-Rhino-Laryngology, Charles Nicolle Hospital, Tunis, Tunisia) for their critical reading and grammar corrections |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] Pharmacology Parasite load Mice parasite load 0302 clinical medicine MESH: Animals Leishmania major MESH: Th1 Cells/immunology Mice Inbred BALB C MESH: Leishmaniasis Cutaneous/drug therapy MESH: Tyrosine/analogs & derivatives 3. Good health [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Infectious Diseases 030220 oncology & carcinogenesis Cytokines Leishmania infantum Injections Subcutaneous lipophilic tyrosyl ester Antiprotozoal Agents MESH: Mice Inbred BALB C Leishmaniasis Cutaneous MESH: Antiprotozoal Agents/administration & dosage MESH: Leishmania major/drug effects Biology BALB/c 03 medical and health sciences Cutaneous leishmaniasis In vivo MESH: Tyrosine/pharmacology medicine Animals Immunologic Factors MESH: Mice anti-leishmanial activity MESH: Injections Subcutaneous Th1 Cells biology.organism_classification medicine.disease Leishmania In vitro MESH: Parasite Load MESH: Immunologic Factors/administration & dosage Disease Models Animal 030104 developmental biology Immunology Tyrosine Animal Science and Zoology Parasitology MESH: Cytokines/metabolism MESH: Disease Models Animal |
| Zdroj: | Parasitology Parasitology, Cambridge University Press (CUP), 2016, 143 (12), pp.1615-1620. ⟨10.1017/S0031182016001086⟩ |
| ISSN: | 1469-8161 0031-1820 |
| Popis: | SUMMARYSynthesized 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. |
| Databáze: | OpenAIRE |
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