Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ETHNOPHARMACOLOGICAL RELEVANCE: Cutaneous leishmaniasis is a neglected disease with a high incidence in French Guiana, mainly in the middle and upper Oyapock basin, where Amerindian and some Brazilian people live. The main goals of this work were (i) to assess the knowledge about leishmaniasis in the different populations of the middle and upper Oyapock basin, (ii) to study the therapeutic strategies adopted by people affected by leishmaniasis and (iii) to document the use of phytotherapeutic remedies for leishmaniasis. Knowledge, attitudes and practices (K.A.P.) related to this disease and its treatments have been studied according to cultural group and geographical settlement. Within the Wayãpi group, the evolution of the knowledge of phytoremedies over the last 20 years has been characterised by literature-based comparisons. MATERIALS AND METHODS: A total of 144 questionnaires were administered in all the villages of the upper Oyapock and Camopi basins. Correspondence analyses were used for multivariate analysis. Plant species were identified at the Cayenne Herbarium (CAY). RESULTS: The biomedical concept of leishmaniasis correlates well with the Teko and Wayãpi concepts of kalasapa and kalasapau. Although the vector of this disease was not correctly identified, the most commonly cited aetiology (74.5%) was vector-borne, and related epidemiological schemes correlate well with the one encountered in French Guiana. Theoretically and practically, health centres were the most commonly used resource for diagnostic in instances of leishmaniasis infection (65.9%), independently of the patient's cultural group, along with the use of pharmaceutical drugs (85.3%). Pharmaceuticals were commonly utilised despite the frequent (51.5%) use of phytotherapeutic remedies, alone or in combination with drugs. The most cited medicinal plant species for the treatment of leishmaniasis included Eleutherine bulbosa (Mill.) Urb. (Iridaceae, cited 14 times), Euterpe oleracea Mart. (Arecaceae, 9), Cecropia obtusa Trecul (Cecropiaceae, 8), Jatropha curcas L. (Euphorbiaceae, 7), Ceiba pentandra (L.) Gaertn. (Bombacaceae, 6) and Carica papaya L. (Caricaceae, 6). Multiple correspondence analyses demonstrated that the species used in leishmaniasis remedies are more prone to vary by the user's place of residence than by their cultural origin, which indicates that exchange of knowledge about leishmaniasis remedies has occurred across different cultural groups. Literature-based comparisons between the remedies for leishmaniasis used by the Wayãpi during the 1980s showed a striking evolution, both in terms of diversity of species and number of plants used. The large number of species shared with other Guianese groups argues for intercultural exchange and may explain the majority (57.1%) of the newly used species highlighted in our study. CONCLUSIONS: Leishmaniasis is a well-known disease in the studied area. Phytotherapeutic treatments are still in use, although they are not the main source of remedies, and should undergo pharmacological studies to evaluate their potential therapeutic value.
ISSN: 0378-8741

pasteur-00634597
https://hal-riip.archives-ouvertes.fr/pasteur-00634597
DOI : 10.1016/j.jep.2011.07.044
PUBMED : 21816216

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
IntroductionLeishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now.Methodology/Principles findingsWe subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%±23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five distinct clusters. They further showed a species-dependent clustering between viral genomes of L. (V.) guyanensis and L. (V.) braziliensis, confirming a long-term co-evolutionary history. Noteworthy, we identified cases of multiple LRV1 infections in three of the 20 Leishmania isolates.Conclusions/SignificanceHere, we present the first-ever estimate of LRV1 genomic diversity that exists in Leishmania (V.) guyanensis parasites. Genetic characterization and phylogenetic analyses of these viruses has shed light on their evolutionary relationships. To our knowledge, this study is also the first to report cases of multiple LRV1 infections in some parasites. Finally, this work has made it possible to develop molecular tools for adequate identification and genotyping of LRV1 strains for diagnostic purposes. Given the suspected worsening role of LRV1 infection in the pathogenesis of human leishmaniasis, these data have a major impact from a clinical viewpoint and for the management of Leishmania-infected patients.
ISSN: 1935-2727

pasteur-01583523
https://hal-riip.archives-ouvertes.fr/pasteur-01583523
DOI : 10.1371/journal.pntd.0005764
PUBMED : 28715422

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
UNLABELLED: During visceral leishmaniasis, the control of hepatic parasite burden is mainly due to granuloma assembly in a microenvironment consisting of both Th1 and Th2 components. Using enzyme-linked immunosorbent assay (ELISA) dosages, quantitative PCR (qPCR), immunohistochemistry, and flow cytometry, we studied the role of interleukin-33 (IL-33), a recently described cytokine signaling through the ST2 receptor, during visceral leishmaniasis. We showed that a higher level of IL-33 was detected in the serum of patients with visceral leishmaniasis than in that from healthy donors and demonstrated the presence of IL-33(+) cells in a liver biopsy specimen from a patient. Similarly, in BALB/c mice experimentally infected with L. donovani, a higher level of IL-33 was detected in the serum, as well as the presence of IL-33(+) cells and ST2(+) cells in the mouse liver. In ST2(-/-) BALB/c mice, better control of the hepatic parasite burden and reduced hepatomegaly were observed. This was associated with strong induction of Th1 cytokines (gamma interferon [IFN-γ] and IL-12) compared to the level in wild-type (WT) mice and better recruitment of myeloid cells associated with strongly induced chemokines (CCL2 and CXCL2) and receptors (CCR2 and CXCR2). Conversely, BALB/c mice treated twice weekly with recombinant IL-33 showed a dramatically reduced induction of Th1 cytokines and delayed inhibition of monocyte and neutrophil recruitment in the liver, which was associated with reduced KC/CXCL1 and CXCR2 expression. Taken together, our results suggest that IL-33 could be a new deleterious regulator of the hepatic immune response against Leishmania donovani, via the repression of the Th1 response and myeloid cell recruitment. IMPORTANCE: Visceral leishmaniasis is a life-threatening systemic disease due to the Leishmania protozoa L. infantum and L. donovani and is ranked by the World Health Organization as the second most important protozoan parasitic disease after malaria for its grave morbidity, high mortality, and global distribution. Leishmania parasites subvert the host's immune response to propagate to target organs, including the spleen, the bone marrow, and the liver. Control of hepatic parasite burdens depends on a delicate and poorly understood Th1/Th2 immune balance. To better understand this complex immune response, new cytokines are interesting targets for research studies. IL-33 is a newly described cytokine usually associated with Th2 response and involved in different diseases, including infectious diseases and hepatitis. Our results suggest that IL-33 could be a new factor of susceptibility and a potential prognostic marker during visceral leishmaniasis.
ISSN: 2150-7511

inserm-00871493
http://www.hal.inserm.fr/inserm-00871493
http://www.hal.inserm.fr/inserm-00871493/document
http://www.hal.inserm.fr/inserm-00871493/file/mBio.00383-13.pdf
DOI : 10.1128/mBio.00383-13

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Les leishmanioses sont des maladies parasitaires à transmission vectorielle observées sur tous les continents, à l’exception de l’Amérique du Nord et de l’Australie. Nous focaliserons ici sur la leishmaniose viscérale méditerranéenne due à Leishmania infantum et dont l’incidence annuelle est estimée entre 1200 et 2000 cas. Son cycle biologique est zoonotique avec un réservoir animal essentiellement canin. Les récentes observations épidémiologiques sont rapportées ici, notamment la mise en évidence du portage humain asymptomatique et l’extension de la zone endémique de la leishmaniose canine. La prise en charge thérapeutique de la leishmaniose viscérale méditerranéenne du patient immunocompétent fait essentiellement appel à l’amphotéricine B liposomale. Le débat existe toujours sur la pertinence d’une prophylaxie secondaire ou des traitements itératifs à chaque rechute chez le patient co-infecté par le VIH. Summary Leishmaniasis are protozoan infections transmitted by the bite of the sandflies, widely reported except in North-America and Australia. Here, we focus on mediterranean visceral leishmaniasis due to Leishmania infantum, with an estimated annual incidence of 1200–2000 cases. Its biological cycle is zoonotic and mainly involves the canine reservoir. The recent epidemiological observations are reported here, particularly the asymptomatic carriage but also the extension of the canine enzooty. Regarding treatment of immunocompetent patients, the drug of choice for mediterranean visceral leishmaniasis is liposomal amphotericin B. In case of HIV-Leishmania co-infection, the interest of secondary prophylaxis is still in debate
ISSN: 2210-6545

hal-01225489
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225489
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225489/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225489/file/Mise%20au%20point%20et%20actualit%C3%A9s%20sur%20la%20leishmaniose%20visc%C3%A9rale%20m%C3%A9diterran%C3%A9enne.pdf
DOI : 10.1016/j.antinf.2014.12.005

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis,which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature andextent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understandsome aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of aL. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility.In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generateslow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. Noantimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensisgenomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmaniaclones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing thecosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasitesare able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populationswith different potentialities to grow lesions during the next infection round. This may reflect a sort of programmedheterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01557855
https://hal-univ-perp.archives-ouvertes.fr/hal-01557855
DOI : 10.1590/0074-02760160280

Éditeur(s) : HAL CCSD
Résumé : International audience
Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (ATL). Such complications are seen frequently in L.guyanensis infections where patients respond variously to first-line anti-leishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently ,: we reported that a dsRNA virus (LRV1) nested within L.guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyper-inflammatory response. This report investigates the prevalence of LRV1 in human L.guyanensis infection and its effect on treatment efficacy as well as its correlation to symptomatic relapses after the first-line treatment. In our cohort of 75 patients diagnosed with primary-localised ATL, the prevalence of LRV1+ infection was elevated to 58%. All patients infected with LRV1-negative L.guyanensis were cured after one (22/31 i.e.71%) or two (31/31 i.e.100%) doses of pentamidine. Oppositely, 12 out of the 44 LRV1-positive patients presented with persistent infection and symptomatic relapse required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in intra-lesional inflammatory markers. In conclusion, LRV1 status in L.guyanensis infection is significantly predictive (p=0.0009) of first-line treatment failure and symptomatic relapse, and could stand to guide therapeutic choices in ATL
Journal of Infectious Diseases

hal-01175528
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01175528
DOI : 10.1093/infdis/jiv355
PUBMED : 26123564

Éditeur(s) : HAL CCSD
Résumé : Visceral leishmaniasis is a life-threatening systemic disease caused by Leishmania protozoans, L. donovani and L. infantum, which invade mononuclear phagocytes in the lymphoid organs and the liver. The control of the hepatic parasite burden depends on the granuloma formation, which is favored by a Th1 immune response in a Th2 tissue microenvironment. The aim of this work was to study the role of the recently described Th2 cytokine IL-33 in this complex immune response, which remains partially misunderstood. IL-33 dosages in different patient sera and IL-33+ cells detected in the liver of a patient from Rennes suggested that IL-33 could be a biomarker for active visceral leishmaniasis. As IL-33 was described in hepatic stellate cells during chronic hepatitis, these cells were exposed to L. donovani in primary culture. The cell permissivity to L. donovani and the parasite persistence during a long term culture led us to propose hepatic stellate cells as a new type of sanctuary cells, which could partially explain asymptomatic carriage. However, these cells were apparently not the main source of IL-33 during visceral leishmaniasis. In infected BALB/c and C57BL/6 mice, IL-33 was detected in the liver in non stellate cells preferentially localized in granulomas. The presence of cells expressing its specific receptor ST2 in the liver led us to explore the role of the IL-33/ST2 axis. BALB/c mice deficient in ST2 or treated with recombinant IL-33 and infected with L. donovani revealed that IL-33 downregulates the expression of Th1 key cytokines (IL-12, IFN-γ) and the recruitment of neutrophils and monocytes. Finally, IL-33 acts as a susceptibility factor during visceral leishmaniasis. Besides, the model of L. donovani infected C57BL/6 mice deficient in IL-33 or treated with recombinant IL-33 suggests possible differential roles of IL-33 depending on the immune environment related to the host genetic background.
La leishmaniose viscérale est une maladie systémique mortelle en l’absence de traitement. Elle est due aux protozoaires Leishmania donovani et L. infantum, parasites des phagocytes mononucléés, capables d’envahir les organes lymphoïdes et le foie. Le contrôle de l’infection hépatique repose sur la mise en place d’une réponse granulomateuse efficace, promue par une réponse immunitaire Th1, dans un environnement tissulaire Th2. L’objectif de ce travail était l'étude du rôle d’une cytokine Th2 récemment décrite, l’IL-33, dans cette réponse hépatique complexe encore partiellement incomprise. Des dosages d’IL-33 sur des sérums de patients et la détection de cellules IL-33+ dans le foie d’un patient rennais ont placé l’IL-33 comme un biomarqueur possible de la maladie active. L’IL-33 étant exprimée dans les cellules étoilées du foie au cours d’hépatites chroniques, ces cellules ont été exposées à L. donovani. Leur permissivité aux leishmanies sans toxicité apparente ni perturbation de leurs propriétés fonctionnelles, ainsi que la persistance des leishmanies sur une culture de plusieurs semaines, nous ont conduit à proposer les cellules étoilées comme cellules sanctuaires possibles pour les leishmanies viscérotropes, contribuant donc potentiellement au portage asymptomatique. En revanche, elles ne sont pas apparues comme une source majeure d'IL-33 au cours de la leishmaniose viscérale. Chez des souris C57BL/6 et BALB/c infectées par L. donovani, l'IL-33 a été observée dans des cellules ne s'apparentant pas à des cellules étoilées, et principalement localisées dans les granulomes. Des cellules exprimant son récepteur ST2 ayant été également observées dans le foie, un rôle de l’axe IL-33/ST2 a été recherché. Les résultats obtenus chez des souris BALB/c déficientes en ST2 ou traitées par de l'IL-33 recombinante suggèrent que l'IL-33 régule négativement l'expression de cytokines Th1 (IL-12, IFN-γ) et l'infiltrat de neutrophiles et monocytes dans le foie, limitant ainsi le contrôle de la charge parasitaire. Ainsi, l'IL-33 semble être un facteur de susceptibilité pour la leishmaniose viscérale. En parallèle, des travaux entrepris sur des souris C57BL/6 infectées par L. donovani suggèrent de possibles rôles différentiels de l'IL-33 en fonction de l'environnement immunitaire inhérent au fond génétique de l'hôte.
https://tel.archives-ouvertes.fr/tel-01126847

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B002
tel-01126847
https://tel.archives-ouvertes.fr/tel-01126847
https://tel.archives-ouvertes.fr/tel-01126847/document
https://tel.archives-ouvertes.fr/tel-01126847/file/2013REN1B002.pdf

Éditeur(s) : HAL CCSD Cambridge University Press (CUP)
Résumé : International audience
Leishmania parasites can escape the immune response by invading cell types lacking leishmanicidal mechanisms. Silent persistence of Leishmania parasites in the host organism is responsible for asymptomatic carriage and relapses after cured leishmaniasis. Here, we studied the interaction between Hepatic Stellate Cells (HSC) and Leishmania. An original model of human HSC in primary culture infected with L. donovani was developed. The presence of intracellular parasites was studied and quantified using optical and confocal microscopy. HSC characteristics were studied using microscopy, methylene blue assay, long-term cultures and qPCR. We showed for the first time that human HSC are permissive to L. donovani infection, with no modification of HSC survival, growth rate and proinflammatory and fibrogenic characteristics. Intracellular parasites did not replicate but HSC had no effect on their survival. Indeed, after a 40-day culture, infected HSC cultures transferred on NNN medium yielded new promastigotes that were able to proliferate and efficiently infect new cells. HSC are permissive to L. donovani, with neither parasite killing nor apparent cell damage. Thus, HSC could act as potent sanctuary cells for Leishmania in the liver, which could partially explain parasite reactivation after an asymptomatic carriage or a cured visceral leishmaniasis.
ISSN: 0031-1820

inserm-00825803
http://www.hal.inserm.fr/inserm-00825803
DOI : 10.1017/S0031182012001965
PUBMED : 23253952

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01489008
https://hal-univ-perp.archives-ouvertes.fr/hal-01489008

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01489009
https://hal-univ-perp.archives-ouvertes.fr/hal-01489009

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
ISSN: 0074-0276

hal-01489007
https://hal-univ-perp.archives-ouvertes.fr/hal-01489007

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Human leishmaniasis are widely spread diseases with different clinical forms caused by about 20 species within the Leishmania genus. Leishmania species identification is relevant for therapeutic management and prognosis, especially for cutaneous and muco-cutaneous forms. Several methods are available to identify Leishmania species from culture, but they have not been standardized for the majority of the currently described species, with the exception of MultiLocus Enzyme Electrophoresis. Moreover, these techniques are expensive, time-consuming and not available in all laboratories. Within the last decade, mass spectrometry (MS) has been adapted for microorganism identification, including Leishmania However, no commercial reference mass spectral database is available. In this study, a reference mass spectral library (MSL) for Leishmania isolates, accessible through a free web-based application (mass spectral identification, MSI), was constructed and tested. It includes mass spectral data for 33 different Leishmania species, including species that infect humans, animals and phlebotomine vectors. Four laboratories on two continents evaluated MSI performance using 268 samples of which 231 were Leishmania strains. All Leishmania strains, but one, were correctly identified at least at the complex level. A risk of species misidentification within the L. donovani, L. guyanensis and L. braziliensis complexes was observed, as already reported with other techniques. The tested application was reliable, with identification results comparable to those obtained with reference methods, but with a more favorable cost-efficiency ratio. This free online identification system relies on a scalable database and can be implemented directly in the user's computers.
ISSN: 0095-1137

hal-01571305
https://hal.archives-ouvertes.fr/hal-01571305
DOI : 10.1128/JCM.00845-17
PUBMED : 28724559

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The parasitic life cycle of Leishmania includes an extracellular promastigote stage that occurs in the gut of the insect vector. During that period, the sucrose metabolism and more specifically the first glycosidase of this pathway are essential for growth and survival of the parasite. We investigated the expression of the invertase BfrA in the promastigote and amastigote stages of three parasite species representative of the three various clinical forms and of various geographical areas, namely Leishmania major, L. donovani and L. braziliensis. Thereafter, we cloned, overexpressed and biochemically characterized this invertase BfrA from L. major, heterologously expressed in both Escherichia coli and L. tarentolae. For all species, expression levels of BfrA mRNA were correlated to the time of the culture and the parasitic stage (promastigotes > amastigotes). BfrA exhibited no activity when expressed as a glycoprotein in L. tarentolae but proved to be an invertase when not glycosylated, yet owing low sequence homology with other invertases from the same family. Our data suggest that BfrA is an original invertase that is located inside the parasite. It is expressed in both parasitic stages, though to a higher extent in promastigotes. This work provides new insight into the parasite sucrose metabolism
ISSN: 0008-6215

hal-01187142
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187142
DOI : 10.1016/j.carres.2015.07.001
PUBMED : 26279524

Résumé : Les études écologiques sont maintenant considérées comme prometteuses en raison de leur capacité à intégrer dans un même modèle autant des facteurs individuels que populationnels. Le mouvement récent de l’open data pourrait jouer un rôle important dans la pérennisation des démarches multidisciplinaires. Cette thèse montre que l’association des méthodes écologiques aux données publiques permet d’éclairer sous un angle nouveau des problématiques des maladies infectieuses.En Guyane Française, des méthodes écologiques dites de séries temporelles couplées aux données climatiques libres ont contribué à une meilleure compréhension du rôle du climat sur la dynamique de la transmission du paludisme, de la leishmaniose cutanée ainsi que de l’histoplasmose disséminée. L’utilisation de méthodes écologiques sur des données libres de la littérature scientifique concernant la séroprévalence toxoplasmose dans les populations humaines a permis d’identifier les principaux facteurs influençant le niveau de séroprévalence globale et indirectement du risque de toxoplasmose congénital associé. L’association de données onusiennes à des méthodes écologiques a permis de montrer qu’une prévalence importante d’ascaridiose est associée à une réduction par 10 de l’incidence du paludisme et l’impact significatif de la corruption sur la mortalité juvéno-infantile et sur les résistances aux anti-tuberculeux. Ces études montrent que l’association des méthodes écologiques aux données publiques permet d’éclairer sous un angle nouveau des problématiques des maladies infectieuses. Ce type d‘étude fournit la flexibilité nécessaire à l’étude des interactions complexes des nombreux déterminants de la santé.
Ecological studies are now considered promising because of their ability to integrate as well as individual factors than populational ones in the same model. The recent open data movement could play an important role in the sustainability of multidisciplinary approaches. The studies developed in this thesis show that the combination of ecological methods with open data could give original results in the issues of infectious diseases.In French Guiana, ecological methods called time series, coupled with open climate data, have contributed to a better understanding of the role of climate on the dynamics of malaria, cutaneous leishmaniasis and disseminated histoplasmosis. The use of ecological methods with open data from the scientific literature concerning toxoplasmosis seroprevalence in human populations has permitted to identify the main factors influencing the level of overall seroprevalence and indirectly to estimate the associated risk of congenital toxoplasmosis.The combination of UN data to ecological methods has shown that a high prevalence of ascariasis is associated with a reduction from 10 in the incidence of malaria and that corruption has a significant impact on child mortality and resistance to TB.The various studies developed in this thesis show that the combination of ecological methods to public data sheds a new light on the issues of infectious diseases. This type of study provides the flexibility to study the complex interactions of many determinants of health.

http://www.theses.fr/2011AGUY0482/document

Éditeur(s) : HAL CCSD
Résumé : After a review of knowledge, attitudes and practices related to leishmaniasis in Amazonia, this work focused on the vegetal species used for its cure. Utilization of geographic and cultural diffusion index allowed to characterize Pan-Amazonian antileishmanial taxa and to investigate the mechanisms allowing for their diffusion. Consistency between traditional use and laboratory results were looked for. Two " knowledge, attitudes and practices " surveys were conducted amongst the Chayahuita (Peru) and along the upper and middle Oyapock river (French Guiana, Teko and Wayãpi groups). These allowed us to refine the knowledge and perception of the disease in these cultural groups, to define patterns in the therapeutic itinerary, and to make an inventory of antileishmanial plant species. Thirty one species used by the Chayahuita were collected and submitted to in vitro assays on axenic amastigotes of Leishmania amazonensis. Pseudoelephantopus spicatus (Asteraceae) is one of the most active and most frequently used plant. From this species, piptocarphol derivatives, very active against Leishmania in vitro, were isolated along with ursolic acid. Presence of these molecules justifies the use of this species as traditional antileishmanial remedy by the Chayahuita.
Après avoir dressé un inventaire des connaissances, attitudes et pratiques concernant les leishmanioses en Amazonie d'après la littérature, le présent travail s'est focalisé sur les espèces végétales connues et utilisées dans le traitement de ces maladies. L'utilisation d'indices de diffusion (géographique, culturelle) a permis de caractériser des taxons antileishmaniens panamazoniens et de définir certains mécanismes impliqués dans leur diffusion. Des cohérences entre usages traditionnels et résultats de laboratoire ont été recherchés. Deux enquêtes de type " connaissance, attitudes et pratiques " effectuées au sein du groupe chayahuita (Pérou), et sur le haut et moyen cours du fleuve Oyapock (Guyane, communautés teko et wayãpi) ont permis d'affiner les connaissances sur la perception de cette maladie dans ces différents groupes culturels, de comprendre les recours aux différentes thérapeutiques et de dresser un inventaire des espèces médicinales utilisées. Trente et une espèces collectées chez les Chayahuita ont été soumises à des essais in vitro sur amastigotes axéniques de Leishmania amazonensis. Pseudoelephantopus spicatus (Asteraceae) compte parmi les espèces les plus actives et les plus fréquemment utilisées, et des dérivés du piptocarphol très actifs sur les parasites in vitro ont été isolés conjointement à l'acide ursolique. La présence de ces molécules permet de justifier en partie l'usage de cette espèce comme antileishmanien traditionnel par les Chayahuita.
https://tel.archives-ouvertes.fr/tel-00590977

tel-00590977
https://tel.archives-ouvertes.fr/tel-00590977
https://tel.archives-ouvertes.fr/tel-00590977/document
https://tel.archives-ouvertes.fr/tel-00590977/file/ThA_se_Odonne_light.pdf