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Albert Descoteaux - One of the best experts on this subject based on the ideXlab platform.
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Leishmania Promastigotes: building a safe niche within macrophages.
Frontiers in Cellular and Infection Microbiology, 2012Co-Authors: Neda Morandini, Albert DescoteauxAbstract:Upon their internalization by macrophages, Leishmania Promastigotes inhibit phagolysosome biogenesis. The main factor responsible for this inhibition is the Promastigote surface glycolipid lipophosphoglycan (LPG). This glycolipid has a profound impact on the phagosome, causing periphagosomal accumulation of F-actin and disruption of phagosomal lipid microdomains. Functionally, this LPG-mediated inhibition of phagosome maturation is characterized by an impaired assembly of the NADPH oxidase and the exclusion of the vesicular proton-ATPase from phagosomes. In this chapter, we review the current knowledge concerning the nature of the intra-macrophage compartment in which Leishmania donovani Promastigotes establish infection. We also describe how LPG enables this parasite to remodel the parasitophorous vacuole.
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leishmania donovani Promastigotes evade the antimicrobial activity of neutrophil extracellular traps
BMC Proceedings, 2011Co-Authors: Christelle Gabriel, Denis Girard, Robert W Mcmaster, Albert DescoteauxAbstract:Upon their recruitment to a site of infection and their subsequent activation, neutrophils release DNA and a subset of their granule content to form filamentous structures, known as neutrophil extracellular traps, which capture and kill microorganisms. In this study, we show that Leishmania Promastigotes induced the rapid release of neutrophil extracellular traps from human neutrophils and were trapped by these structures. The use of Leishmania mutants defective in the biosynthesis of either lipophosphoglycan or GP63 revealed that these two major surface Promastigote virulence determinants were not responsible for inducing the release of neutrophil extracellular traps. We also demonstrate that this induction was independent of superoxide production by neutrophils. Finally, in contrast to wild type L. donovani Promastigotes, mutants defective in lipophosphoglycan biosynthesis were highly susceptible to the antimicrobial activity of neutrophil extracellular traps. Altogether, our data suggest that neutrophil extracellular traps may contribute to the containment of L. donovani Promastigotes at the site of inoculation, thereby facilitating their uptake by mononuclear phagocytes.
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Leishmania donovani Promastigotes evade the antimicrobial activity of neutrophil extracellular traps.
Journal of Immunology, 2010Co-Authors: Christelle Gabriel, W Robert Mcmaster, Denis Girard, Albert DescoteauxAbstract:Upon their recruitment to a site of infection and their subsequent activation, neutrophils release DNA and a subset of their granule content to form filamentous structures, known as neutrophil extracellular traps, which capture and kill microorganisms. In this study, we show that Leishmania Promastigotes induced the rapid release of neutrophil extracellular traps from human neutrophils and were trapped by these structures. The use of Leishmania mutants defective in the biosynthesis of either lipophosphoglycan or GP63 revealed that these two major surface Promastigote virulence determinants were not responsible for inducing the release of the surface protease neutrophil extracellular traps. We also demonstrate that this induction was independent of superoxide production by neutrophils. Finally, in contrast to wild-type Leishmania donovani Promastigotes, mutants defective in lipophosphoglycan biosynthesis were highly susceptible to the antimicrobial activity of neutrophil extracellular traps. Altogether, our data suggest that neutrophil extracellular traps may contribute to the containment of L. donovani Promastigotes at the site of inoculation, thereby facilitating their uptake by mononuclear phagocytes.
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Modulation of phagolysosome biogenesis by the lipophosphoglycan of Leishmania.
Clinical immunology (Orlando Fla.), 2005Co-Authors: Robert Lodge, Albert DescoteauxAbstract:Promastigotes of the protozoan parasite Leishmania are inoculated into the mammalian host by an infected sandfly and are phagocytosed by macrophages. There, they differentiate into amastigotes, which replicate in phagolysosomes. A family of glycoconjugates, the phosphoglycans (PGs), plays an important role in the ability of Promastigotes to survive the potentially microbicidal consequences of phagocytosis. Lipophosphoglycan (LPG), an abundant Promastigote surface glycolipid, has received considerable attention over the past several years. Of interest for this review, lipophosphoglycan confers upon Leishmania donovani Promastigotes the ability to inhibit phagolysosome biogenesis. This inhibition correlates with an accumulation of periphagosomal F-actin, which may potentially form a physical barrier that prevents L. donovani Promastigote-harboring phagosomes from interacting with late endosomes and lysosomes. Thus, similar to several other pathogens, Leishmania Promastigotes hijack the host cell's cytoskeleton early during the infection process. Here, we review this phenomenon and discuss the potential underlying mechanisms.
Jesus G Valenzuela - One of the best experts on this subject based on the ideXlab platform.
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distinct gene expression patterns in vector residing leishmania infantum identify parasite stage enriched markers
PLOS Neglected Tropical Diseases, 2020Co-Authors: Iliano V Coutinhoabreu, Tiago D Serafim, Claudio Meneses, Shaden Kamhawi, Fabiano Oliveira, Jesus G ValenzuelaAbstract:Background Leishmaniasis is a vector-borne neglected disease. Inside the natural sand fly vector, the Promastigote forms of Leishmania undergo a series of extracellular developmental stages to reach the infectious stage, the metacyclic Promastigote. There is limited information regarding the expression profile of L. infantum developmental stages inside the sand fly vector, and molecular markers that can distinguish the different parasite stages are lacking. Methodology/principal findings We performed RNAseq on unaltered midguts of the sand fly Lutzomyia longipalpis after infection with L. infantum parasites. RNAseq was carried out at various time points throughout parasite development. Principal component analysis separated the transcripts corresponding to the different Leishmania Promastigote stages, the procyclic, nectomonad, leptomonad and metacyclics. Importantly, there were a significant number of differentially expressed genes when comparing the sequential development of the various Leishmania stages in the sand fly. There were 836 differentially expressed (DE) genes between procyclic and long nectomonad Promastigotes; 113 DE genes between nectomonad and leptomonad Promastigotes; and 302 DE genes between leptomonad and metacyclic Promastigotes. Most of the DE genes do not overlap across stages, highlighting the uniqueness of each Leishmania stage. Furthermore, the different stages of Leishmania parasites exhibited specific transcriptional enrichment across chromosomes. Using the transcriptional signatures exhibited by distinct Leishmania stages during their development in the sand fly midgut, we determined the genes predominantly enriched in each stage, identifying multiple potential stage-specific markers for L. infantum. Conclusions Overall, these findings demonstrate the transcriptional plasticity of the Leishmania parasite inside the sand fly vector and provide a repertoire of potential stage-specific markers for further development as molecular tools for epidemiological studies.
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distinct gene expression patterns in vector residing leishmania infantum identify parasite stage enriched markers
bioRxiv, 2019Co-Authors: Iliano V Coutinhoabreu, Tiago D Serafim, Claudio Meneses, Shaden Kamhawi, Fabiano Oliveira, Jesus G ValenzuelaAbstract:Promastigotes of Leishmania infantum undergo a series of extracellular developmental stages inside the natural sand fly vector Lutzomyia longipalpis to reach the infectious stage, the metacyclic Promastigote. There is limited information regarding the expression profile of L. infantum developmental stages inside the sand fly vector, and molecular markers that can distinguish the different parasite stages are lacking. We performed RNAseq on unaltered midguts of the sand fly Lutzomyia longipalpis after infection with L. infantum parasites. RNAseq was carried out at various time points throughout parasite development. Principal component analysis mapped the sequences corresponding to the procyclic, nectomonad, leptomonad or metacyclic Promastigote stage into distinct positions, with the procyclic stage being the most divergent population. Transcriptional levels across genes varied on average between 10- to 100-fold. Comparison between procyclic and nectomonad Promastigotes resulted in 836 differentially expressed (DE) genes; between nectomonad and leptomonad Promastigotes in 113 DE genes; and between leptomonad and metacyclic Promastigotes in 302 DE genes. Most of the DE genes do not overlap across stages, highlighting the uniqueness of each stage. Furthermore, the different stages of Leishmania parasites exhibited specific transcriptional enrichment across chromosomes. Using the transcriptional signatures exhibited by distinct Leishmania stages during their development in the sand fly midgut, we determined the genes predominantly enriched in each stage, identifying multiple stage-specific markers for L. Infantum . Leading stage-specific marker candidates include genes encoding a zinc transporter in procyclics, a beta-fructofuranidase in nectomonads, a surface antigen-like protein in leptomonads, and an amastin-like surface protein in metacyclics. Overall, these findings demonstrate the transcriptional plasticity of the Leishmania parasite inside the sand fly vector and provide a repertoire of stage-specific markers for further development as molecular tools for epidemiological studies.
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sequential blood meals promote leishmania replication and reverse metacyclogenesis augmenting vector infectivity
Nature microbiology, 2018Co-Authors: Tiago D Serafim, Iliano V Coutinhoabreu, Claudio Meneses, Shaden Kamhawi, Fabiano Oliveira, Jesus G ValenzuelaAbstract:Sand flies, similar to most vectors, take multiple blood meals during their lifetime1-4. The effect of subsequent blood meals on pathogens developing in the vector and their impact on disease transmission have never been examined. Here, we show that ingestion of a second uninfected blood meal by Leishmania-infected sand flies triggers dedifferentiation of metacyclic Promastigotes, considered a terminally differentiated stage inside the vector 5 , to a leptomonad-like stage, the retroleptomonad Promastigote. Reverse metacyclogenesis occurs after every subsequent blood meal where retroleptomonad Promastigotes rapidly multiply and differentiate to metacyclic Promastigotes enhancing sand fly infectiousness. Importantly, a subsequent blood meal amplifies the few Leishmania parasites acquired by feeding on infected hosts by 125-fold, and increases lesion frequency by fourfold, in twice-fed compared with single-fed flies. These findings place readily available blood sources as a critical element in transmission and propagation of vector-borne pathogens.
Iliano V Coutinhoabreu - One of the best experts on this subject based on the ideXlab platform.
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distinct gene expression patterns in vector residing leishmania infantum identify parasite stage enriched markers
PLOS Neglected Tropical Diseases, 2020Co-Authors: Iliano V Coutinhoabreu, Tiago D Serafim, Claudio Meneses, Shaden Kamhawi, Fabiano Oliveira, Jesus G ValenzuelaAbstract:Background Leishmaniasis is a vector-borne neglected disease. Inside the natural sand fly vector, the Promastigote forms of Leishmania undergo a series of extracellular developmental stages to reach the infectious stage, the metacyclic Promastigote. There is limited information regarding the expression profile of L. infantum developmental stages inside the sand fly vector, and molecular markers that can distinguish the different parasite stages are lacking. Methodology/principal findings We performed RNAseq on unaltered midguts of the sand fly Lutzomyia longipalpis after infection with L. infantum parasites. RNAseq was carried out at various time points throughout parasite development. Principal component analysis separated the transcripts corresponding to the different Leishmania Promastigote stages, the procyclic, nectomonad, leptomonad and metacyclics. Importantly, there were a significant number of differentially expressed genes when comparing the sequential development of the various Leishmania stages in the sand fly. There were 836 differentially expressed (DE) genes between procyclic and long nectomonad Promastigotes; 113 DE genes between nectomonad and leptomonad Promastigotes; and 302 DE genes between leptomonad and metacyclic Promastigotes. Most of the DE genes do not overlap across stages, highlighting the uniqueness of each Leishmania stage. Furthermore, the different stages of Leishmania parasites exhibited specific transcriptional enrichment across chromosomes. Using the transcriptional signatures exhibited by distinct Leishmania stages during their development in the sand fly midgut, we determined the genes predominantly enriched in each stage, identifying multiple potential stage-specific markers for L. infantum. Conclusions Overall, these findings demonstrate the transcriptional plasticity of the Leishmania parasite inside the sand fly vector and provide a repertoire of potential stage-specific markers for further development as molecular tools for epidemiological studies.
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distinct gene expression patterns in vector residing leishmania infantum identify parasite stage enriched markers
bioRxiv, 2019Co-Authors: Iliano V Coutinhoabreu, Tiago D Serafim, Claudio Meneses, Shaden Kamhawi, Fabiano Oliveira, Jesus G ValenzuelaAbstract:Promastigotes of Leishmania infantum undergo a series of extracellular developmental stages inside the natural sand fly vector Lutzomyia longipalpis to reach the infectious stage, the metacyclic Promastigote. There is limited information regarding the expression profile of L. infantum developmental stages inside the sand fly vector, and molecular markers that can distinguish the different parasite stages are lacking. We performed RNAseq on unaltered midguts of the sand fly Lutzomyia longipalpis after infection with L. infantum parasites. RNAseq was carried out at various time points throughout parasite development. Principal component analysis mapped the sequences corresponding to the procyclic, nectomonad, leptomonad or metacyclic Promastigote stage into distinct positions, with the procyclic stage being the most divergent population. Transcriptional levels across genes varied on average between 10- to 100-fold. Comparison between procyclic and nectomonad Promastigotes resulted in 836 differentially expressed (DE) genes; between nectomonad and leptomonad Promastigotes in 113 DE genes; and between leptomonad and metacyclic Promastigotes in 302 DE genes. Most of the DE genes do not overlap across stages, highlighting the uniqueness of each stage. Furthermore, the different stages of Leishmania parasites exhibited specific transcriptional enrichment across chromosomes. Using the transcriptional signatures exhibited by distinct Leishmania stages during their development in the sand fly midgut, we determined the genes predominantly enriched in each stage, identifying multiple stage-specific markers for L. Infantum . Leading stage-specific marker candidates include genes encoding a zinc transporter in procyclics, a beta-fructofuranidase in nectomonads, a surface antigen-like protein in leptomonads, and an amastin-like surface protein in metacyclics. Overall, these findings demonstrate the transcriptional plasticity of the Leishmania parasite inside the sand fly vector and provide a repertoire of stage-specific markers for further development as molecular tools for epidemiological studies.
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sequential blood meals promote leishmania replication and reverse metacyclogenesis augmenting vector infectivity
Nature microbiology, 2018Co-Authors: Tiago D Serafim, Iliano V Coutinhoabreu, Claudio Meneses, Shaden Kamhawi, Fabiano Oliveira, Jesus G ValenzuelaAbstract:Sand flies, similar to most vectors, take multiple blood meals during their lifetime1-4. The effect of subsequent blood meals on pathogens developing in the vector and their impact on disease transmission have never been examined. Here, we show that ingestion of a second uninfected blood meal by Leishmania-infected sand flies triggers dedifferentiation of metacyclic Promastigotes, considered a terminally differentiated stage inside the vector 5 , to a leptomonad-like stage, the retroleptomonad Promastigote. Reverse metacyclogenesis occurs after every subsequent blood meal where retroleptomonad Promastigotes rapidly multiply and differentiate to metacyclic Promastigotes enhancing sand fly infectiousness. Importantly, a subsequent blood meal amplifies the few Leishmania parasites acquired by feeding on infected hosts by 125-fold, and increases lesion frequency by fourfold, in twice-fed compared with single-fed flies. These findings place readily available blood sources as a critical element in transmission and propagation of vector-borne pathogens.
Christelle Gabriel - One of the best experts on this subject based on the ideXlab platform.
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leishmania donovani Promastigotes evade the antimicrobial activity of neutrophil extracellular traps
BMC Proceedings, 2011Co-Authors: Christelle Gabriel, Denis Girard, Robert W Mcmaster, Albert DescoteauxAbstract:Upon their recruitment to a site of infection and their subsequent activation, neutrophils release DNA and a subset of their granule content to form filamentous structures, known as neutrophil extracellular traps, which capture and kill microorganisms. In this study, we show that Leishmania Promastigotes induced the rapid release of neutrophil extracellular traps from human neutrophils and were trapped by these structures. The use of Leishmania mutants defective in the biosynthesis of either lipophosphoglycan or GP63 revealed that these two major surface Promastigote virulence determinants were not responsible for inducing the release of neutrophil extracellular traps. We also demonstrate that this induction was independent of superoxide production by neutrophils. Finally, in contrast to wild type L. donovani Promastigotes, mutants defective in lipophosphoglycan biosynthesis were highly susceptible to the antimicrobial activity of neutrophil extracellular traps. Altogether, our data suggest that neutrophil extracellular traps may contribute to the containment of L. donovani Promastigotes at the site of inoculation, thereby facilitating their uptake by mononuclear phagocytes.
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Leishmania donovani Promastigotes evade the antimicrobial activity of neutrophil extracellular traps.
Journal of Immunology, 2010Co-Authors: Christelle Gabriel, W Robert Mcmaster, Denis Girard, Albert DescoteauxAbstract:Upon their recruitment to a site of infection and their subsequent activation, neutrophils release DNA and a subset of their granule content to form filamentous structures, known as neutrophil extracellular traps, which capture and kill microorganisms. In this study, we show that Leishmania Promastigotes induced the rapid release of neutrophil extracellular traps from human neutrophils and were trapped by these structures. The use of Leishmania mutants defective in the biosynthesis of either lipophosphoglycan or GP63 revealed that these two major surface Promastigote virulence determinants were not responsible for inducing the release of the surface protease neutrophil extracellular traps. We also demonstrate that this induction was independent of superoxide production by neutrophils. Finally, in contrast to wild-type Leishmania donovani Promastigotes, mutants defective in lipophosphoglycan biosynthesis were highly susceptible to the antimicrobial activity of neutrophil extracellular traps. Altogether, our data suggest that neutrophil extracellular traps may contribute to the containment of L. donovani Promastigotes at the site of inoculation, thereby facilitating their uptake by mononuclear phagocytes.
Robert B Tesh - One of the best experts on this subject based on the ideXlab platform.
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life cycle of leishmania major kinetoplastida trypanosomatidae in the neotropical sand fly lutzomyia longipalpis diptera psychodidae
Journal of Medical Entomology, 1993Co-Authors: Laurel L Walters, Katherine P Irons, Gertrude L Chaplin, Robert B TeshAbstract:The development of Leishmania major Yakimoff & Schokhor in the New World sand fly Lutzomyia longipalpis (Lutz & Neiva) was examined by light and electron microscopy. In this unnatural host, parasites differentiated into 10 typical morphological forms, multiplied at three sites, migrated anteriorly and established in the foregut, and attached to gut surfaces. In the blood meal, amastigotes divided and transformed into two successive dividing, stumpy Promastigote stages. Elongate nectomonad Promastigotes developed from stumpy forms and subsequently rounded up in some flies into paramastigotes and opisthomastigotes. Differentiation into round opisthomastigotes and the apparent fusion of paramastigotes in the blood meal were novel observations in this study. Three nectomonad Promastigotes--elongate, short, and metacyclic--were free-swimming in the midgut lumen. Elongate nectomonad Promastigotes were highly oriented in the midgut, with their flagella embedded between the epithelial microvilli. Short haptomonad Promastigotes were the predominant form attached to the intima of the stomodeal valve, whereas pear-shaped haptomonad Promastigotes and paramastigotes colonized surfaces of the esophagus and pharynx. Peripylarian attachment of Promastigotes and paramastigotes in the pylorus, ileum, and colon was noted in 21% of flies, suggesting that suprapylarian leishmanias have not lost the ability to colonize the hindgut. L. longipalpis was a successful biological host for L. major, allowing complete development of the parasite.
