The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
Shaden Kamhawi - One of the best experts on this subject based on the ideXlab platform.
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Unique Features of Vector-Transmitted Leishmaniasis and Their Relevance to Disease Transmission and Control
Arthropod Vector: Controller of Disease Transmission Volume 2, 2017Co-Authors: Tiago D. Serafim, Jesus G Valenzuela, Ranadhir Dey, Hira L. Nakhasi, Shaden KamhawiAbstract:Abstract Leishmania transmission garnered attention due to the virulence of these vector-transmitted parasites. Numerous studies established a remarkable complexity to the infectious inoculum of an infected sand Fly Bite. Parasites, though they are the etiological agents of leishmaniasis, are but one of several components with potent immunomodulatory properties that shape the immune environment at the Bite site. To date, known components include saliva, the parasite secretory gel, and exosomes. Sand Fly vector-derived virulence factors are only of consequence in the context of parasite delivery by Bite. All of these components participate in creating a milieu that favors parasite establishment. Understanding the immunological consequences of an infected sand Fly Bite will improve our understanding of disease pathogenesis, and they have implications for novel approaches to leishmaniasis control.
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What's behind a sand Fly Bite? The profound effect of sand Fly saliva on host hemostasis, inflammation and immunity.
Infection genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2014Co-Authors: Maha Abdeladhim, Shaden Kamhawi, Jesus G ValenzuelaAbstract:Sand flies are blood-feeding insects and vectors of the Leishmania parasite. For many years, saliva of these insects has represented a gold mine for the discovery of molecules with anti-hemostatic and immuno-modulatory activities. Furthermore, proteins in sand Fly saliva have been shown to be a potential vaccine against leishmaniasis and also markers of vector exposure. A bottleneck to progress in these areas of research has been the identification of molecules responsible for the observed activities and properties of saliva. Over the past decade, rapid advances in transcriptomics and proteomics resulted in the completion of a number of sialomes (salivary gland transcriptomes) and the expression of several recombinant salivary proteins from different species of sand Fly vectors. This review will provide readers with a comprehensive update of recent advances in the characterization of these salivary molecules and their biological activities and offer insights pertaining to their protective effect against leishmaniasis and their potential as markers of vector exposure.
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characterization of the early inflammatory infiltrate at the feeding site of infected sand flies in mice protected from vector transmitted leishmania major by exposure to uninfected Bites
PLOS Neglected Tropical Diseases, 2014Co-Authors: Clarissa Teixeira, Jesus G Valenzuela, Regis Gomes, Dia Eldin Elnaiem, Fabiano Oliveira, Claudio Meneses, Dana C Gilmore, Shaden KamhawiAbstract:BACKGROUND: Mice exposed to sand Fly saliva are protected against vector-transmitted Leishmania major. Although protection has been related to IFN-I³ producing T cells, the early inflammatory response orchestrating this outcome has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: Mice exposed to uninfected P. duboscqi Bites and naive mice were challenged with L. major-infected flies to characterize their early immune response at the Bite site. Mostly, chemokine and cytokine transcript expression post-infected Bites was amplified in exposed compared to naive mice. In exposed mice, induced chemokines were mostly involved in leukocyte recruitment and T cell and NK cell activation; IL-4 was expressed at 6 h followed by IFN-I³ and iNOS2 as well as IL-5 and IL-10 expression. In naive animals, the transcript expression following Leishmania-infected sand Fly Bites was suppressed. Expression profiles translated to an earlier and significantly larger recruitment of leukocytes including neutrophils, macrophages, Gr+ monocytes, NK cells and CD4+ T cells to the Bite site of exposed compared to naive mice post-infected Bites. Additionally, up to 48 hours post-infected Bites the number of IFN-I³-producing CD4+ T cells and NK cells arriving at the Bite site was significantly higher in exposed compared to naive mice. Thereafter, NK cells become cytolytic and persist at the Bite site up to a week post-Bite. CONCLUSION/SIGNIFICANCE: The quiet environment induced by a Leishmania-infected sand Fly Bite in naive mice was significantly altered in animals previously exposed to saliva of uninfected flies. We propose that the enhanced recruitment of Gr+ monocytes, NK cells and CD4 Th1 cells observed at the Bite site of exposed mice creates an inhospitable environment that counters the establishment of L. major infection
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vector transmission of leishmania abrogates vaccine induced protective immunity
PLOS Pathogens, 2009Co-Authors: Nathan C Peters, Phillip G Lawyer, Shaden Kamhawi, Nicola Kimblin, Nagila Secundino, David L SacksAbstract:Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand Fly Bite. The only immunization strategy known to protect humans against natural exposure is “leishmanization,” in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand Fly Bite within 24 hours, and these mice were highly resistant to sand Fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM)+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand Fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand Fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania.
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sand Fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral leishmaniasis with adverse consequences for leishmania
PLOS Pathogens, 2009Co-Authors: Nicolas Collin, Jesus G Valenzuela, Regis Gomes, Clarissa Teixeira, Lily I Cheng, Andre Laughinghouse, Jerrold M Ward, Dia Eldin Elnaiem, Laurent Fischer, Shaden KamhawiAbstract:Immunity to a sand Fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-γ at the site of sand Fly Bites. To date, there are no data available regarding the cellular immune response to sand Fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand Fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG2 antibody levels and significant IFN-γ production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the Bite site characterized by lymphocytic infiltration and IFN-γ and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand Fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand Fly Bite and set the stage for a protective anti-Leishmania immune response.
Guy Caljon - One of the best experts on this subject based on the ideXlab platform.
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Neutrophils enhance early Trypanosoma brucei infection onset
Scientific Reports, 2018Co-Authors: Guy Caljon, Dorien Mabille, Benoit Stijlemans, Carl De Trez, Massimiliano Mazzone, Fabienne Tacchini-cottier, Marie Malissen, Jo A. Van Ginderachter, Stefan Magez, Patrick De BaetselierAbstract:In this study, Trypanosoma brucei was naturally transmitted to mice through the Bites of infected Glossina morsitans tsetse flies. Neutrophils were recruited rapidly to the Bite site, whereas monocytes were attracted more gradually. Expression of inflammatory cytokines (il1b, il6), il10 and neutrophil chemokines (cxcl1, cxcl5) was transiently up-regulated at the site of parasite inoculation. Then, a second influx of neutrophils occurred that coincided with the previously described parasite retention and expansion in the ear dermis. Congenital and experimental neutropenia models, combined with bioluminescent imaging, indicate that neutrophils do not significantly contribute to dermal parasite control and elicit higher systemic parasitemia levels during the infection onset. Engulfment of parasites by neutrophils in the skin was rarely observed and was restricted to parasites with reduced motility/viability, whereas live parasites escaped phagocytosis. To our knowledge, this study represents the first description of a trypanosome infection promoting role of early innate immunological reactions following an infective tsetse Fly Bite. Our data indicate that the trypanosome is not hindered in its early development and benefits from the host innate responses with the neutrophils being important regulators of the early infection, as already demonstrated for the sand Fly transmitted Leishmania parasite.
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Serological responses and biomarker evaluation in mice and pigs exposed to tsetse Fly Bites.
PLOS Neglected Tropical Diseases, 2014Co-Authors: Guy Caljon, Reta Duguma, Reginald De Deken, Stijn Schauvliege, Luc Duchateau, Frank Gasthuys, Jan Van Den AbbeeleAbstract:Background Tsetse flies are obligate blood-feeding insects that transmit African trypanosomes responsible for human sleeping sickness and nagana in livestock. The tsetse salivary proteome contains a highly immunogenic family of the endonuclease-like Tsal proteins. In this study, a recombinant version of Tsal1 (rTsal1) was evaluated in an indirect ELISA to quantify the contact with total Glossina morsitans morsitans saliva, and thus the tsetse Fly Bite exposure.
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Serological responses and biomarker evaluation in mice and pigs exposed to tsetse Fly Bites.
PLoS neglected tropical diseases, 2014Co-Authors: Guy Caljon, Reta Duguma, Reginald De Deken, Stijn Schauvliege, Luc Duchateau, Frank Gasthuys, Jan Van Den AbbeeleAbstract:Tsetse flies are obligate blood-feeding insects that transmit African trypanosomes responsible for human sleeping sickness and nagana in livestock. The tsetse salivary proteome contains a highly immunogenic family of the endonuclease-like Tsal proteins. In this study, a recombinant version of Tsal1 (rTsal1) was evaluated in an indirect ELISA to quantify the contact with total Glossina morsitans morsitans saliva, and thus the tsetse Fly Bite exposure. Mice and pigs were experimentally exposed to different G. m. morsitans exposure regimens, followed by a long-term follow-up of the specific antibody responses against total tsetse Fly saliva and rTsal1. In mice, a single tsetse Fly Bite was sufficient to induce detectable IgG antibody responses with an estimated half-life of 36-40 days. Specific antibody responses could be detected for more than a year after initial exposure, and a single Bite was sufficient to boost anti-saliva immunity. Also, plasmas collected from tsetse-exposed pigs displayed increased anti-rTsal1 and anti-saliva IgG levels that correlated with the exposure intensity. A strong correlation between the detection of anti-rTsal1 and anti-saliva responses was recorded. The ELISA test performance and intra-laboratory repeatability was adequate in the two tested animal models. Cross-reactivity of the mouse IgGs induced by exposure to different Glossina species (G. m. morsitans, G. pallidipes, G. palpalis gambiensis and G. fuscipes) and other hematophagous insects (Stomoxys calcitrans and Tabanus yao) was evaluated. This study illustrates the potential use of rTsal1 from G. m. morsitans as a sensitive biomarker of exposure to a broad range of Glossina species. We propose that the detection of anti-rTsal1 IgGs could be a promising serological indicator of tsetse Fly presence that will be a valuable tool to monitor the impact of tsetse control efforts on the African continent.
David L Sacks - One of the best experts on this subject based on the ideXlab platform.
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the role of dermis resident macrophages and their interaction with neutrophils in the early establishment of leishmania major infection transmitted by sand Fly Bite
bioRxiv, 2020Co-Authors: Mariana M Chaves, Olena Kamenyeva, Kashinath Ghosh, David L SacksAbstract:There is substantial experimental evidence to indicate that Leishmania infections that are transmitted naturally by the Bites of infected sand flies differ in fundamental ways from the inflammatory and immune reactions initiated by needle inocula. We have used flow cytometry and intravital microscopy (IVM) to reveal the heterogeneity of sand Fly transmission sites with respect to the subsets of phagocytes in the skin that harbor L. major within the first hours and days after infection. By flow cytometry analysis, dermis resident macrophages (TRMs) were on average the predominant infected cell type at 1 hr and 24 hr. By confocal IVM, the co-localization of L. major and neutrophils varied depending on the proximity of deposited parasites to the presumed site of vascular damage, defined by the highly localized swarming of neutrophils. Some of the dermal TRMs could be visualized acquiring their infections via transfer from or efferocytosis of parasitized neutrophils, providing direct evidence for the “Trojan Horse” model. The role of neutrophil engulfment by dermal TRMs and the involvement of the Tyro3/Axl/Mertk family of receptor tyrosine kinases in these interactions and in sustaining the anti-inflammatory program of dermal TRMs was supported by the effects observed in neutrophil depleted and in Axl -/- Mertk -/- mice. The Axl -/- Mertk -/- mice also displayed reduced parasite burdens but more severe pathology following L. major infection transmitted by sand Fly Bite.
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evaluation of recombinant leishmania polyprotein plus glucopyranosyl lipid a stable emulsion vaccines against sand Fly transmitted leishmania major in c57bl 6 mice
Journal of Immunology, 2012Co-Authors: Nathan C Peters, Flavia L Ribeirogomes, Sylvie Bertholet, Phillip G Lawyer, Melanie Charmoy, Audrey Romano, Lisa Stamper, David L SacksAbstract:Numerous experimental Leishmania vaccines have been developed to prevent the visceral and cutaneous forms of Leishmaniasis, which occur after exposure to the Bite of an infected sand Fly, yet only one is under evaluation in humans. KSAC and L110f, recombinant Leishmania polyproteins delivered in a stable emulsion (SE) with the TLR4 agonists monophosphoryl lipid A or glucopyranosyl lipid A (GLA) have shown protection in animal models. KSAC+GLA-SE protected against cutaneous disease following sand Fly transmission of Leishmania major in susceptible BALB/c mice. Similar polyprotein adjuvant combinations are the vaccine candidates most likely to see clinical evaluation. We assessed immunity generated by KSAC or L110f vaccination with GLA-SE following challenge with L. major by needle or infected sand Fly Bite in resistant C57BL/6 mice. Polyprotein-vaccinated mice had a 60-fold increase in CD4 + IFN-γ + T cell numbers versus control animals at 2 wk post–needle inoculation of L. major , and this correlated with a 100-fold reduction in parasite load. Immunity did not, however, reach levels observed in mice with a healed primary infection. Following challenge by infected sand Fly Bite, polyprotein-vaccinated animals had comparable parasite loads, greater numbers of neutrophils at the challenge site, and reduced CD4 + IFN-γ + /IL-17 + ratios versus nonvaccinated controls. In contrast, healed animals had significantly reduced parasite loads and higher CD4 + IFN-γ + /IL-17 + ratios. These observations demonstrate that vaccine-induced protection against needle challenge does not necessarily translate to protection following challenge by infected sand Fly Bite.
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the influence of early neutrophil leishmania interactions on the host immune response to infection
Frontiers in Cellular and Infection Microbiology, 2012Co-Authors: Flavia L Ribeirogomes, David L SacksAbstract:Neutrophils are the first cells recruited to the dermal site of Leishmania infection following injection by needle or sand Fly Bite. The role of neutrophils in either promoting or suppressing host immunity remains controversial. We discuss the events driving neutrophil recruitment, their interaction with the parasite and apoptotic fate, and the nature of their encounters with other innate cells. We suggest that the influence of the neutrophil response on infection outcome critically depends on the timing of their recruitment and the tissue environment in which it occurs.
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The impact of vector-mediated neutrophil recruitment on cutaneous leishmaniasis.
Cellular microbiology, 2009Co-Authors: Nathan C Peters, David L SacksAbstract:The dynamic process of pathogen transmission by the Bite of an insect vector combines several biological processes that have undergone extensive co-evolution. Whereas the host response to an insect Bite is only occasionally confronted with the parasitic pathogens that competent vectors might transmit, the transmitted parasites will always be confronted with the acute, wound-healing response that is initiated by the Bite itself. Invariably, this response involves neutrophils. In the case of Leishmania, infection is initiated in the skin following the Bite of an infected sand Fly, suggesting that Leishmania must possess some means to survive their early encounter with recruited neutrophils at the Bite site. Here, we review the literature regarding the impact of neutrophils on the outcome of infection with Leishmania, with special attention to the role of the sand Fly Bite.
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vector transmission of leishmania abrogates vaccine induced protective immunity
PLOS Pathogens, 2009Co-Authors: Nathan C Peters, Phillip G Lawyer, Shaden Kamhawi, Nicola Kimblin, Nagila Secundino, David L SacksAbstract:Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand Fly Bite. The only immunization strategy known to protect humans against natural exposure is “leishmanization,” in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand Fly Bite within 24 hours, and these mice were highly resistant to sand Fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM)+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand Fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand Fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania.
Jesus G Valenzuela - One of the best experts on this subject based on the ideXlab platform.
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Unique Features of Vector-Transmitted Leishmaniasis and Their Relevance to Disease Transmission and Control
Arthropod Vector: Controller of Disease Transmission Volume 2, 2017Co-Authors: Tiago D. Serafim, Jesus G Valenzuela, Ranadhir Dey, Hira L. Nakhasi, Shaden KamhawiAbstract:Abstract Leishmania transmission garnered attention due to the virulence of these vector-transmitted parasites. Numerous studies established a remarkable complexity to the infectious inoculum of an infected sand Fly Bite. Parasites, though they are the etiological agents of leishmaniasis, are but one of several components with potent immunomodulatory properties that shape the immune environment at the Bite site. To date, known components include saliva, the parasite secretory gel, and exosomes. Sand Fly vector-derived virulence factors are only of consequence in the context of parasite delivery by Bite. All of these components participate in creating a milieu that favors parasite establishment. Understanding the immunological consequences of an infected sand Fly Bite will improve our understanding of disease pathogenesis, and they have implications for novel approaches to leishmaniasis control.
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Neutrophil recruitment during Leishmania infection: The role of sand Fly salivary proteins
Journal of Immunology, 2016Co-Authors: Anderson Guimaraes, Jesus G Valenzuela, Xi Wen, Augusto Marcelino Carvalho, Joseph A. Brzostowski, Fabiano OliveiraAbstract:Neutrophils are the first cells recruited to the site of an infected sand Fly Bite and interact with Leishmania parasites. It has been proposed that the recruitment of neutrophils to the site of the Bite increases the ability of Leishmania to establish an infection. Here we investigate the effect of sand Fly salivary proteins on neutrophil recruitment. We purified bone marrow neutrophils from C57BL/6 mice or from peripheral blood of healthy human donors. Chemotaxis driven by sand Fly saliva of vectors of visceral ( Lutzomyia longipalpis ) or cutaneous ( Phlebotomus duboscqi ) disease was measured by modified Boyden chamber assay and by imaging with the EZ-TAXIScan assay. Neutrophils migrated towards saliva glands of the vectors P. duboscqi and L. longipalpis , in a dose-dependent manner. Proteinase K treatment of saliva completely abrogated neutrophil recruitment, suggesting a protein as the chemotactic factor. To unearth the identity of the chemotactic factor, we have generated plasmids coding for the 20 most abundant salivary proteins from P. duboscqi and injected them in the ears of C57BL/6 mice. Neutrophil recruitment was analyzed by flow cytometry staining. We have identified 3 different salivary protein-coding plasmids with neutrophil recruitment activity. Finally, we have produced these 3 recombinant proteins in the HEK293 cell line system and we observed that a family of 40kDa salivary proteins acts as chemokines for neutrophils. We plan to validate the role of the salivary chemotactic factor in vivo and test if its neutralization can alter Leishmania infection. We put forward the hypothesis that blockage of this protein will disrupt neutrophil migration early in the Leishmania infection possibly altering the disease outcome.
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What's behind a sand Fly Bite? The profound effect of sand Fly saliva on host hemostasis, inflammation and immunity.
Infection genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2014Co-Authors: Maha Abdeladhim, Shaden Kamhawi, Jesus G ValenzuelaAbstract:Sand flies are blood-feeding insects and vectors of the Leishmania parasite. For many years, saliva of these insects has represented a gold mine for the discovery of molecules with anti-hemostatic and immuno-modulatory activities. Furthermore, proteins in sand Fly saliva have been shown to be a potential vaccine against leishmaniasis and also markers of vector exposure. A bottleneck to progress in these areas of research has been the identification of molecules responsible for the observed activities and properties of saliva. Over the past decade, rapid advances in transcriptomics and proteomics resulted in the completion of a number of sialomes (salivary gland transcriptomes) and the expression of several recombinant salivary proteins from different species of sand Fly vectors. This review will provide readers with a comprehensive update of recent advances in the characterization of these salivary molecules and their biological activities and offer insights pertaining to their protective effect against leishmaniasis and their potential as markers of vector exposure.
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characterization of the early inflammatory infiltrate at the feeding site of infected sand flies in mice protected from vector transmitted leishmania major by exposure to uninfected Bites
PLOS Neglected Tropical Diseases, 2014Co-Authors: Clarissa Teixeira, Jesus G Valenzuela, Regis Gomes, Dia Eldin Elnaiem, Fabiano Oliveira, Claudio Meneses, Dana C Gilmore, Shaden KamhawiAbstract:BACKGROUND: Mice exposed to sand Fly saliva are protected against vector-transmitted Leishmania major. Although protection has been related to IFN-I³ producing T cells, the early inflammatory response orchestrating this outcome has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: Mice exposed to uninfected P. duboscqi Bites and naive mice were challenged with L. major-infected flies to characterize their early immune response at the Bite site. Mostly, chemokine and cytokine transcript expression post-infected Bites was amplified in exposed compared to naive mice. In exposed mice, induced chemokines were mostly involved in leukocyte recruitment and T cell and NK cell activation; IL-4 was expressed at 6 h followed by IFN-I³ and iNOS2 as well as IL-5 and IL-10 expression. In naive animals, the transcript expression following Leishmania-infected sand Fly Bites was suppressed. Expression profiles translated to an earlier and significantly larger recruitment of leukocytes including neutrophils, macrophages, Gr+ monocytes, NK cells and CD4+ T cells to the Bite site of exposed compared to naive mice post-infected Bites. Additionally, up to 48 hours post-infected Bites the number of IFN-I³-producing CD4+ T cells and NK cells arriving at the Bite site was significantly higher in exposed compared to naive mice. Thereafter, NK cells become cytolytic and persist at the Bite site up to a week post-Bite. CONCLUSION/SIGNIFICANCE: The quiet environment induced by a Leishmania-infected sand Fly Bite in naive mice was significantly altered in animals previously exposed to saliva of uninfected flies. We propose that the enhanced recruitment of Gr+ monocytes, NK cells and CD4 Th1 cells observed at the Bite site of exposed mice creates an inhospitable environment that counters the establishment of L. major infection
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sand Fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral leishmaniasis with adverse consequences for leishmania
PLOS Pathogens, 2009Co-Authors: Nicolas Collin, Jesus G Valenzuela, Regis Gomes, Clarissa Teixeira, Lily I Cheng, Andre Laughinghouse, Jerrold M Ward, Dia Eldin Elnaiem, Laurent Fischer, Shaden KamhawiAbstract:Immunity to a sand Fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-γ at the site of sand Fly Bites. To date, there are no data available regarding the cellular immune response to sand Fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand Fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG2 antibody levels and significant IFN-γ production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the Bite site characterized by lymphocytic infiltration and IFN-γ and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand Fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand Fly Bite and set the stage for a protective anti-Leishmania immune response.
Daniel K Masiga - One of the best experts on this subject based on the ideXlab platform.
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trypanosoma brucei rhodesiense transmitted by a single tsetse Fly Bite in vervet monkeys as a model of human african trypanosomiasis
PLOS Neglected Tropical Diseases, 2008Co-Authors: John K Thuita, J M Kagira, David Mumo Mwangangi, Enock Matovu, C M R Turner, Daniel K MasigaAbstract:We have investigated the pathogenicity of tsetse (Glossina pallidipes)-transmitted cloned strains of Trypanosoma brucei rhodesiense in vervet monkeys. Tsetse flies were confirmed to have mature trypanosome infections by xenodiagnosis, after which nine monkeys were infected via the Bite of a single infected Fly. Chancres developed in five of the nine (55.6%) monkeys within 4 to 8 days post infection (dpi). All nine individuals were successfully infected, with a median pre-patent period of 4 (range = 4–10) days, indicating that trypanosomes migrated from the site of Fly Bite to the systemic circulation rapidly and independently of the development of the chancre. The time lag to detection of parasites in cerebrospinal fluid (CSF) was a median 16 (range = 8–40) days, marking the onset of central nervous system (CNS, late) stage disease. Subsequently, CSF white cell numbers increased above the pre-infection median count of 2 (range = 0–9) cells/µl, with a positive linear association between their numbers and that of CSF trypanosomes. Haematological changes showed that the monkeys experienced an early microcytic-hypochromic anaemia and severe progressive thrombocytopaenia. Despite a 3-fold increase in granulocyte numbers by 4 dpi, leucopaenia occurred early (8 dpi) in the monkey infection, determined mainly by reductions in lymphocyte numbers. Terminally, leucocytosis was observed in three of nine (33%) individuals. The duration of infection was a median of 68 (range = 22–120) days. Strain and individual differences were observed in the severity of the clinical and clinical pathology findings, with two strains (KETRI 3741 and 3801) producing a more acute disease than the other two (KETRI 3804 and 3928). The study shows that the Fly-transmitted model accurately mimics the human disease and is therefore a suitable gateway to understanding human African trypanosomiasis (HAT; sleeping sickness).