Recent updates and perspectives on leishmaniasis

Savoia, Dianella

doi:10.3855/jidc.6833

Cited by 144 publications

(148 citation statements)

References 70 publications

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“…Leishmaniosis is one of the most important parasitic diseases in the world (1,2). This disease is a complex infection caused by several species of Leishmania genus belonged to family Trypanosomatidae, subfamily Leishmaniinae (3).…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and Efficacy of Polytope DNA Vaccine Against Cutaneous Leishmaniosis In Vivo

et al. 2017

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Background: About 12 million people are affected by les leishmaniosis worldwide. It is an important public health problem due to the difficulty in its control and causing epidemic outbreaks. An effective anti-leishmanial vaccine remains elusive. Isolated dominant epitopes arranged as polytope DNA vaccine represent a promising approach. Methods: Balb/c mice were vaccinated subcutaneously with pCDNA3.1/LAKJB93 DNA and challenged with Leishmania major promastigotes; then, the level of interferon (INF)-γ and interleukin (IL)-4 were measured by the enzyme-linked immunosorbent assay (ELISA) technique. Production of immunoglobulin (Ig)-G1 and IgG2a antigen specific antibodies were measured against LAKJB93. Results: The enhanced production of antigen-specific INF-γ and IgG2a in serum showed the stimulation of T helper type 1 (Th1) response. This protective immune response was induced by the expression of pcDNA3.1/ LAKJB93 plasmid against leishmaniosis and therefore, pcDNA3.1/ LAKJB93 can be considered an appropriate vaccine for leishmaniosis. Conclusions: Immunization with DNA vaccine may offer an effective route to prevent leishmaniosis.

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Section: Introductionmentioning

confidence: 99%

Immunogenicity and Efficacy of Polytope DNA Vaccine Against Cutaneous Leishmaniosis In Vivo

et al. 2017

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“…In the digestive tract of their vector, parasites transform back into extracellular promastigotes that develop into infectious metacyclics (2). Depending on the status of the host immune system and the Leishmania species, the infection of mammals leads either to mostly self-healing skin lesions (cutaneous leishmaniasis [CL]) or to a systemic disease, termed visceral leishmaniasis (VL) or kala-azar, that is lethal if untreated (3)(4)(5).…”

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confidence: 99%

Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by Leishmania major via the Exosome Pathway

et al. 2017

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Similar to other intracellular pathogens, Leishmania parasites are known to evade the antimicrobial effector functions of host immune cells. To date, however, only a few virulence factors have been described for Leishmania major, one of the causative agents of cutaneous leishmaniasis. Here, we have characterized the expression and function of an L. major phosphatase, which we termed LmPRL-1. This enzyme shows a strong structural similarity to the human phosphatases of regenerating liver (PRL-1, -2, and -3) that regulate the proliferation, differentiation, and motility of cells. The biochemical characterization of the L. major phosphatase revealed that the enzyme is redox sensitive. When analyzing the subcellular localization of LmPRL-1 in promastigotes, amastigotes, and infected macrophages, we found that the phosphatase was predominantly expressed and secreted by promastigotes via the exosome route. Finally, we observed that ectopic expression of LmPRL-1 in L. major led to an increased number of parasites in macrophages. From these data, we conclude that the L. major phosphatase LmPRL-1 contributes to the intracellular survival of the parasites in macrophages.KEYWORDS Leishmania, exosome, macrophage, tyrosine phosphatase L eishmaniasis is an infectious disease prevalent worldwide that is caused by kinetoplastid protozoan parasites belonging to the genus Leishmania (1). In nature, this heteroxenous parasite is transmitted by the bites of sand flies. Following the inoculation of flagellated promastigotes into the dermis of the host, the parasites are rapidly endocytosed by phagocytic cells, in which they differentiate into amastigotes, multiply, and reach inner compartments and organs, such as draining lymph nodes, spleen, liver, and bone marrow. The life cycle of the parasite is completed after ingestion of amastigote-infected cells by sand flies during their blood meal. In the digestive tract of their vector, parasites transform back into extracellular promastigotes that develop into infectious metacyclics (2). Depending on the status of the host immune system and the Leishmania species, the infection of mammals leads either to mostly self-healing skin lesions (cutaneous leishmaniasis [CL]) or to a systemic disease, termed visceral leishmaniasis (VL) or kala-azar, that is lethal if untreated (3-5).To survive in their hosts, Leishmania parasites need to quickly adapt their growth, metabolism, and mechanisms of protection to their new environment. Interestingly, only a few genes are differentially expressed during this adaptive process, suggesting an important role for the regulation of protein translation (6). Leishmania speciesspecific gene diversity also participates in the adaptation of the parasite to its organ-

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“…Depending on the species of Leishmania involved, the infection can affect the skin and mucous membranes (cutaneous leishmaniasis [CL]) or the internal organs (visceral leishmaniasis [VL]) (1,2). Official estimates point to an annual incidence of approximately 300,000 VL cases and 1.0 million CL cases worldwide (3).…”

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confidence: 99%

Antileishmanial Activity of Ezetimibe: Inhibition of Sterol Biosynthesis, In Vitro Synergy with Azoles, and Efficacy in Experimental Cutaneous Leishmaniasis

Andrade-Neto

Cunha-Júnior

Canto‐Cavalheiro

et al. 2016

Antimicrob Agents Chemother

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Leishmaniasis affects mainly low-income populations in tropical regions. Radical innovation in drug discovery is time-consuming and expensive, imposing severe restrictions on the ability to launch new chemical entities for the treatment of neglected diseases. Drug repositioning is an attractive strategy for addressing a specific demand more easily. In this project, we have evaluated the antileishmanial activities of 30 drugs currently in clinical use for various morbidities. Ezetimibe, clinically used to reduce intestinal cholesterol absorption in dyslipidemic patients, killed Leishmania amazonensis promastigotes with a 50% inhibitory concentration (IC 50 ) of 30 M. Morphological analysis revealed that ezetimibe caused the parasites to become rounded, with multiple nuclei and flagella. Analysis by gas chromatography (GC)-mass spectrometry (MS) showed that promastigotes treated with ezetimibe had smaller amounts of C-14-demethylated sterols, and accumulated more cholesterol and lanosterol, than untreated promastigotes. We then evaluated the combination of ezetimibe with well-known antileishmanial azoles. The fractional inhibitory concentration index (FICI) indicated synergy when ezetimibe was combined with ketoconazole or miconazole. The activity of ezetimibe against intracellular amastigotes was confirmed, with an IC 50 of 20 M, and ezetimibe reduced the IC 90 s of ketoconazole and miconazole from 11.3 and 11.5 M to 4.14 and 8.25 M, respectively. Subsequently, we confirmed the activity of ezetimibe in vivo, showing that it decreased lesion development and parasite loads in murine cutaneous leishmaniasis. We concluded that ezetimibe has promising antileishmanial activity and should be considered in combination with azoles in further preclinical and clinical studies.

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Recent updates and perspectives on leishmaniasis

Cited by 144 publications

References 70 publications

Immunogenicity and Efficacy of Polytope DNA Vaccine Against Cutaneous Leishmaniosis In Vivo

Immunogenicity and Efficacy of Polytope DNA Vaccine Against Cutaneous Leishmaniosis In Vivo

Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by Leishmania major via the Exosome Pathway

Antileishmanial Activity of Ezetimibe: Inhibition of Sterol Biosynthesis, In Vitro Synergy with Azoles, and Efficacy in Experimental Cutaneous Leishmaniasis

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