Antileishmanial effect of rapamycin as an alternative approach to control Leishmania tropica infection

Publication date: Available online 10 November 2019Source: Veterinary ParasitologyAuthor(s): Fatemeh Khadir, Tahereh Taheri, Sima Habibzadeh, Farnaz Zahedifard, Elham Gholami, Maryam Heidari-Kharaji, Ahmad Oryan, Sima RafatiAbstractCutaneous leishmaniosis (CL) is a parasitic disease in animals and human with no satisfactory treatments and vaccination. Rapamycin is a potent inhibitor of mammalian target of rapamycin (mTOR) with various applications. Here, the effect of rapamycin alone or in combination with two other drugs, namely amphotericin B (AmB) and glucantime, was investigated against Leishmania tropica infection. In vitro viability and electron microscopy evaluation of the parasites showed detrimental changes in their appearance and viability. Treatment with clinically relevant dose of rapamycin (10.2 µg/dose) is able to control the parasite load in BALB/c mice infected with L. tropica. Furthermore, the cytokine profiles showed significant polarization towards Th1 immune response. Surprisingly, combination therapy with either AmB or glucantime was not efficient. Rapamycin is showed an effective alternative therapy against leishmaniosis caused by L. tropica.Graphical abstract
Source: Veterinary Parasitology - Category: Veterinary Research Source Type: research

Related Links:

In conclusion, LPGs from dermotropic strains are devoid of side-chains and exhibit high pro-inflammatory activity. PMID: 32965329 [PubMed - in process]
Source: Memorias do Instituto Oswaldo Cruz - Category: Infectious Diseases Authors: Tags: Mem Inst Oswaldo Cruz Source Type: research
Abstract Visceral leishmaniasis (VL) is a systemic infection caused by the protozoal parasite Leishmania, spread via the bloodstream to the reticuloendothelial system, through the bite of the sand fly. It is endemic in parts of Africa, South America, Asia, and Europe, including the Mediterranean. Here, we describe a case of VL that was initially diagnosed as Q fever based on positive Coxiella burnetii serology and showed a partial response to doxycycline treatment. PMID: 32959758 [PubMed - as supplied by publisher]
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
This study further highlights the complex links betweenL.tropica important genomic heterogeneity and the parasite broad geographic distribution. Unique sequence features in protein coding genes identified in distinct populations reveal potential novel markers that could be exploited for the development of more accurate typing schemes to further improve our knowledge of the evolution and epidemiology of the parasite as well as highlighting protein variants of potential functional importance underlyingL.tropica specific biology.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Abstract The kingdom of Saudi Arabia (KSA) has succeeded in bringing the reported numbers of Visceral leishmaniasis (VL) cases from hundreds during the 1980s and 1990s to zero case in 2019. The endemicity of VL has been confined mainly to the Southwest regions, namely Jazan and Aseer regions. Leishmania donovani species have been identified as the causative species of VL, while L. infantum have been isolated only from dogs in the endemic areas. Many species of sand flies were caught in Southwest, but P. orientalis is the probable transmitter of the disease. The black rat (Rattus ratus) was found to be contributing...
Source: Acta Tropica - Category: Infectious Diseases Authors: Tags: Acta Trop Source Type: research
Abstract The clinical course and outcome of cutaneous leishmaniasis (CL) vary due to the infecting Leishmania species and host genetic makeup that result in different immune responses against the parasites. The host immune response to Leishmania aethiopica (L.aethiopica), the causative agent of CL in Ethiopia, is poorly understood. To contribute to the understanding of the protective immune response in CL due to L.aethiopica, we characterized the cytokine response to L. aethiopica in patients with the localized form of CL (LCL) and age-and sex-matched apparently healthy controls. By applying a whole blood based in...
Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research
Platelets are specialized anucleate cells that play a major role in hemostasis following vessel injury. More recently, platelets have also been implicated in innate immunity and inflammation by directly interacting with immune cells and releasing proinflammatory signals. It is likely therefore that in certain pathologies, such as chronic parasitic infections and myeloid malignancies, platelets can act as mediators for hemostatic and proinflammatory responses. Fortunately, murine platelet function ex vivo is highly analogous to human, providing a robust model for functional comparison. However, traditional methods of studyi...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Leishmaniasis is a neglected vector-borne disease caused by an intracellular protozoan parasite belonging to the genus Leishmania spp. (Alvar et al., 2012). Clinical presentations include a broad range of manifestations, ulcerative lesions of cutaneous leishmaniasis (CL), Mucocutaneous Leishmaniasis (ML), and visceral leishmaniasis (VL), also known as kala-azar (Desjeux, 2004). CL is the dominant manifestation and widely distributed worldwide, affecting approximately 1.5 to 2 million new cases each year and 350 million are at risk of acquiring the disease (WHO, 2018; Steverding, 2017).
Source: International Journal of Infectious Diseases - Category: Infectious Diseases Authors: Source Type: research
In this study we demonstrated the potential association effect of conventional amphotericin B (Amph B) and Gallic acid (GA) or Ellagic acid (EA) in topical formulation for treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests and in vitro drug release studies with Amph B, GA, Amph B + GA, EA and Amph B + EA in the composition and in vivo treatment of BALB/c mice infected by Leishmania major were performed. After 40 days of infection, the animals were divided into 6 groups, treated 2x/day, for 21 days with the gel of Amph B, GA, Amph B + GA, EA and Amph B + EA and the negative control group was tr...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract As the causative agent of hard-to-treat diffuse cutaneous leishmaniasis, Leishmania (L.) amazonensis persists in the host organism sheltered within large Parasitophorous Vacuoles (PVs) formed mainly in macrophages. In the present study, I present a simple and efficient method for L. amazonensis PV isolation. Isolated PVs are intact as demonstrated by the conservation of lysosomal probes loaded into PVs before the procedure. The method is useful for studies aiming at a complete and accurate molecular profile of these structures, to better understand the biogenesis of this pathogen-containing vacuole and it...
Source: Experimental Parasitology - Category: Parasitology Authors: Tags: Exp Parasitol Source Type: research
Cutaneous leishmaniasis is a disease caused by the protozoan parasite Leishmania major (L. major) and transferred to humans by infected phlebotomine sand flies. Cutaneous leishmaniasis manifests in lesion formation of the infected skin and poses a severe health burden with 1 million cases reported in the last five years. In healthy individuals and murine experimental leishmaniasis of resistant C57BL/6 mice, cutaneous disease can be controlled via Th1/Tc1-mediated immune responses that are characterized by IFN γ-driven macrophage activation and parasite killing, which induces live-long memory and protection.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Letters to the Editor Source Type: research
More News: Abelcet | Alternative and Complementary Therapies | HIV-Leishmania Co-infection | Parasitic Diseases | Parasitology | Vaccines | Veterinary Research | Veterinary Vaccinations