Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aim of the study: A knowledge attitude and practice study centred on leishmaniasis and its treatment was performed among the Chayahuita, an Amazonian Peruvian ethnic group living in an endemic area. This study documents traditional Chayahuita plant's use and disease concepts. Also, activty of some medicinal plants used by the Chayahuita is highlighted and discussed. Materials and methods: Ninety-three Chayahuita people were interviewed, following a semi-structured questionnaire focussed on disease knowledge and perception, personal attitude and healing practices. Simultaneously, a collection of plants was performed in different ecotopes, in order to make an extensive inventory of the pharmacopoeia. Results: For the Chayahuita, cutaneous (CL) and muco-cutaneous leishmaniasis (MCL) are considered as diseases of their own, with specific names, aetiologies, mode of transmission. Regarding CL, Chayahuita people consider that the humid characteristic of the skin ulcer is a discriminative fact orienting the diagnostic forTa'ta' (leishmaniasis). Forty-six different species were designated useful against LC and /or MCL (29 species by means of the questionnaire and 27 species when collecting in different ecotopes). Thirty-seven extracts corresponding to 31 species used medicinally were screened in vitro against Leishmania amnzonensis axenic amastigotes, assessing their viability by the reduction of tetrazolium salt (MTT). Six species displayed a good activity ( 10 μg/ml < IC50 < 20 μg/ml): an undetermined hemi-epiphytic Clusiaceae, Cyhianthus anthuriophyllus Pipoly (Myrsinaceae), two Piper, Piper sanguineispicum Trel., and Piper loretoanum Trel. (Piperaceae), Desmodium axillare Sw. DC. (Fabaceae), and Clibadium sylvestre (Aubl.) Baill. (Asteraceae). Conclusion: Perception of leishmaniasis, attitude, treatments and diet prohibitions still largely reflects traditional Chayahuita cosmovision, even if some tentative of bio-medical re-interpretation is arising.
ISSN: 0378-8741

hal-01087667
https://hal-agroparistech.archives-ouvertes.fr/hal-01087667
DOI : 10.1016/j.jep.2009.07.015

Éditeur(s) : HAL CCSD
Résumé : International audience
Leishmania parasites induce an immunomodulation by subverting the host immune response towards a CD4(+) Th2 lymphocytic cell response that favors parasite persistence. Here, we report that after successful treatment of visceral leishmaniasis due to Leishmania infantum, an immune reconstitution syndrome revealing hip septic arthritis was associated with a switch from Th2 towards a Th1 cytokine profile, and a decrease in the level of immunomodulating factors, such as soluble HLA-G and indoleamine 2,3-dioxygenase (IDO) activity. We then measured IDO activity in a cohort of 39 patients and uninfected control subjects. Results showed significantly enhanced IDO activity in patients with visceral Leishmania infection, compared with uninfected control subjects (P < 0.001), but also compared with treated patients (P < 0.05). A decrease in IDO activity could constitute a relevant biomarker for the restoration of the immune response during visceral leishmaniasis.
Innate Immunity

inserm-00818884
http://www.hal.inserm.fr/inserm-00818884
DOI : 10.1177/1753425912473170
PUBMED : 23413147

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 European Centre for Disease Prevention and Control
Résumé : International audience
Leishmaniasis is endemic in southern Europe, and in other European countries cases are diagnosed in travellers who have visited affected areas both within the continent and beyond. Prompt and accurate diagnosis poses a challenge in clinical practice in Europe. Different methods exist for identification of the infecting Leishmania species. Sixteen clinical laboratories in 10 European countries, plus Israel and Turkey, conducted a study to assess their genotyping performance. DNA from 21 promastigote cultures of 13 species was analysed blindly by the routinely used typing method. Five different molecular targets were used, which were analysed with PCR-based methods. Different levels of identification were achieved, and either the Leishmania subgenus, species complex, or actual species were reported. The overall error rate of strains placed in the wrong complex or species was 8.5%. Various reasons for incorrect typing were identified. The study shows there is considerable room for improvement and standardisation of Leishmania typing. The use of well validated standard operating procedures is recommended, covering testing, interpretation, and reporting guidelines. Application of the internal transcribed spacer 1 of the rDNA array should be restricted to Old World samples, while the heat-shock protein 70 gene and the mini-exon can be applied globally.
ISSN: 1560-7917

hal-01460743
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01460743
DOI : 10.2807/1560-7917.ES.2016.21.49.30418
PUBMED : 27983510

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
To study the link between climatic variables and the incidence of leishmaniasis a study was conducted in Cayenne, French Guiana. Patients infected between January 1994 and December 2010. Meteorological data were studied in relation to the incidence of leishmaniasis using an ARIMA model. In the final model, the infections were negatively correlated with rainfall (with a 2-month lag) and with the number of days with rainfall > 50 mm (lags of 4 and 7 months). The variables that were positively correlated were temperature and the Multivariate El Niño Southern Oscillation Index with lags of 8 and 4 months, respectively. Significantly greater correlations were observed in March for rainfall and in November for the Multivariate El Niño/Southern Oscillation Index. Climate thus seems to be a non-negligible explanatory variable for the fluctuations of leishmaniasis. A decrease in rainfall is linked to increased cases 2 months later. This easily perceptible point could lead to an interesting prevention message.
ISSN: 0002-9637

inserm-00913933
http://www.hal.inserm.fr/inserm-00913933
http://www.hal.inserm.fr/inserm-00913933/document
http://www.hal.inserm.fr/inserm-00913933/file/article_amaury_leishmaniose_revised2corrected.pdf
http://www.hal.inserm.fr/inserm-00913933/file/figure_2.pdf

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 Elsevier
Résumé : International audience
The non-classical human leukocyte antigen-G, HLA-G, plays an important role in inducing tolerance, through its immunosuppressive effects on all types of immune cells. Immune tolerance is a key issue in the liver, both in liver homeostasis and in the response to liver injury or cancer. It would therefore appear likely that HLA-G plays an important role in liver diseases. Indeed, this molecule was recently shown to be produced by mast cells in the livers of patients infected with hepatitis C virus (HCV). Furthermore, the number of HLA-G-positive mast cells was significantly associated with fibrosis progression. The generation of immune tolerance is a role common to both HLA-G, as a molecule, and the liver, as an organ. This review provides a summary of the evidence implicating HLA-G in liver diseases. In the normal liver, HLA-G transcripts can be detected, but there is no HLA-G protein. However, HLA-G protein is detectable in the liver tissues and/or plasma of patients suffering from hepatocellular carcinoma, hepatitis B or C, or visceral leishmaniasis and in liver transplant recipients. The cells responsible for producing HLA-G differ between diseases. HLA-G expression is probably induced by microenvironmental factors, such as cytokines. The expression of HLA-G receptors, such as ILT2, ILT4, and KIRD2L4, on liver cells has yet to be investigated, but these receptors have been detected on all types of immune cells, and such cells are present in liver. The tolerogenic properties of HLA-G explain its deleterious effects in cancers and its beneficial effects in transplantation. Given the key role of HLA-G in immune tolerance, new therapeutic agents targeting HLA-G could be tested for the treatment of these diseases in the future.
ISSN: 0168-8278

hal-01134468
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134468
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134468/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134468/file/Biology%20of%20the%20immunomodulatory%20molecule%20HLA-G.pdf
DOI : 10.1016/j.jhep.2015.03.007

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 Elsevier
Résumé : Ethnopharmacological relevance: Cutaneous and mucocutaneous leishmaniasis are neglected tropical diseases that occur in all intertropical regions of the world. Amazonian populations have developed an abundant knowledge of the disease and its remedies. Therefore, we undertook to review traditional antileishmanial plants in Amazonia and have developed new tools to analyze this somewhat dispersed information.Material and methods: A literature review of traditional remedies for cutaneous/mucocutaneous leishmaniasis in the Amazon was conducted and the data obtained was used to calculate distribution indexes designed to highlight the most relevant uses in Amazonia. The cultural distribution index represents the distribution rate of a given taxon among different cultural groups and was calculated as the ratio of the number of groups using the taxon to the total number of groups cited. The geographical distribution index allowed us to quantify spatial distribution of a taxon's uses in Amazonia and was calculated geometrically by measuring the average distance between the points where uses have been reported and the barycenter of those points. The general distribution index was defined as an arithmetic combination of the previous two and provides information on both cultural and spatial criteria.Results: 475 use reports, concerning 291 botanical species belonging to 83 families have been gathered depicted from 29 sources. Uses concern 34 cultural groups. While the use of some taxa appears to be Pan Amazonian, some others are clearly restricted to small geographical regions. Particular attention has been paid to the recipes and beliefs surrounding treatments. Topical application of the remedies dominated the other means of administration and this deserves particular attention as the main treatments against Neotropical leishmaniasis are painful systemic injections. The data set was analyzed using the previously defined distribution indexes and the most relevant taxa were further discussed from a phytochemical and pharmacological point of view.Conclusions: The Amazonian biodiversity and cultural heritage host a fantastic amount of data whose systematic investigation should allow a better large-scale understanding of the dynamics of traditional therapies and the consequent discovery of therapeutic solutions for neglected diseases. Distribution indices are indeed powerful tools for emphasizing the most relevant treatments against a given disease and should be very useful in the meta-analysis of other regional pharmacopeia. This focus on renowned remedies that have not yet benefitted from extended laboratory studies, could stimulate future research on new treatments of natural origin for leishmaniasis.
ISSN: 0378-8741

hal-01603285
https://hal.archives-ouvertes.fr/hal-01603285
DOI : 10.1016/j.jep.2017.01.048
PRODINRA : 401890

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 BioMed Central
Résumé : International audience
BACKGROUND:In French Guiana, a French overseas territory in South America, 6 to 10 thousands undocumented persons work illegally in gold mining sites in the Amazonian forest. Precarious life conditions lead to poor health but few data exist on the health status of illegal gold miners in French Guiana. The objective of this article was to describe the sociodemographic and health status of this vulnerable population.METHOD:A prospective cross-sectional survey was conducted in 2015 on gold mine supply sites at the border between French Guiana and Suriname. Health status was assessed through medical examination, past medical history, haemoglobin concentration, and HIV and malaria testing. A questionnaire was used to collect data about the migration itinerary and life conditions on mining sites.RESULTS:Among the 421 adults included in the study, 93.8% (395/421) were Brazilian, mainly from Maranhão (55.7%, 220/395), the poorest Brazilian state. The sex ratio was 2.4. Overall, 48% of persons never went to school or beyond the primary level. The median time spent in gold mining was quite long (10 years), with a high turn-over. One third of the surveyed population (37.1%, 156/421) had high blood pressure, and only two had a medical follow-up. Most persons had experienced malaria (89.3%, 376/421). They declared frequent arboviroses and digestive disorders. Active leishmaniasis was observed in 8.3% of gold miners. Among women, 28.5% were anemic. Concerning HIV, 36.6% (154/421) of persons, mainly men, never got tested before and 6 were tested positive, which represented an HIV prevalence of 1.43% (95%CI =0.29-2.5).CONCLUSION:These findings support the hypothesis that mining in remote areas is linked to several specific illnesses. Theoretically, gold miners would be presumed to start their economical migration to French Guiana as a healthy group. However, their strenuous working and living conditions there lead to poor health caused by infectious and non infectious diseases. This description of their health status is precious for health policy planners in French Guiana given the importance of controlling communicable disease, and the severity and range of specific illnesses acquired by this neglected population.TRIAL REGISTRATION:Clinical trial registration PRS N° NCT02903706 . Retrospectively registered 09/13/2016.
ISSN: 1471-2458

inserm-01566314
http://www.hal.inserm.fr/inserm-01566314
http://www.hal.inserm.fr/inserm-01566314/document
http://www.hal.inserm.fr/inserm-01566314/file/2017%2C%20Douine%20-%20Illegal%20gold%20miners%20in%20French%20Guiana.pdf
DOI : 10.1016/S0140-6736(10)62169-1

Éditeur(s) : HAL CCSD
Résumé : International audience
Studying the ecology of Leishmania parasites is essential for understanding and controlling the epidemiology of the diseases they cause. Despite their abundance and diversity in neotropical forests, few studies have been conducted to investigate the potential involvement of Chiroptera in the Leishmania pathogenic complexes. However, phlebotomine sand flies are known to colonize the same anthropized habitat, are attracted to bats, and are able to transmit trypanosomatids. Thus, 216 bats representing 29 species were sampled in the field in different primary and secondary forests of French Guiana where human cutaneous leishmaniases have been reported, together with 62 non-volant mammals. A series of 411 tissue samples representing 47 mammalian species were cultured and screened for the presence of Leishmania spp. by a genus-specific polymerase chain reaction. All 278 individuals surveyed were negative. Thus, bats do not appear to be involved in the Lishmania parasitic cycles in the Guyanas.
The American journal of tropical medicine and hygiene

halsde-00339305
https://hal.archives-ouvertes.fr/halsde-00339305

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The development of inflammatory granulomas around infected Kupffer cells is necessary for hepatic parasite clearance during visceral leishmaniasis. Invariant NKT (iNKT) cells are predominant T cells in the mouse liver and can synthesize large quantities of IL-4 and IFN-γ, two cytokines involved in granuloma formation. This study analyzed the role of iNKT cells in the hepatic immune response during Leishmania donovani infection, using a murine model of wild-type (WT) and iNKT cell-deficient (Jα18⁻/⁻) C57BL/6 mice sacrificed 15, 30 or 60 days post-infection. We recorded hepatic parasite loads, cytokine expression, and analyzed granulomatous response by immunohistochemistry and hepatic immune cell infiltration by flow cytometry. Whereas WT animals rapidly controlled the infection and developed an inflammatory response associated with a massive influx of iNKT cells observed by flow cytometry, Jα18⁻/⁻ mice had significantly higher parasitic loads on all time points. This lack of control of parasite burden was associated with a delay in granuloma maturation (28.1% of large granulomas at day 60 versus 50.7% in WT). Cytokine transcriptome analysis showed that mRNA of 90/101 genes encoding chemokines, cytokines and their receptors, was underexpressed in Jα18⁻/⁻ mice. Detection of IL-4 and TNF-α by ELISA in liver extracts was also significantly lower in Jα18⁻/⁻ mice. Consistent with flow cytometry analysis, cytokinome profile in WT mice showed a bias of expression towards T cell-chemoattractant chemokines on D15, and displayed a switch towards expression of granulocytes and/or monocytes -chemoattractant chemokines on D60. In Jα18⁻/⁻ mice, the significantly lower expression of CXCL5, MIP-2 and CCL2 mRNA was correlated with a defect in myeloperoxidase positive-cell attraction observed by immunohistochemistry and with a lower granulocyte and monocyte infiltration in the liver, as shown by flow cytometry. These data indicate that iNKT cells play a role in early and sustained pro-inflammatory cytokine response warranting efficient organization of hepatic granulomas and parasite clearance.
ISSN: 1932-6203

hal-00696897
https://hal.archives-ouvertes.fr/hal-00696897
https://hal.archives-ouvertes.fr/hal-00696897/document
https://hal.archives-ouvertes.fr/hal-00696897/file/Invariant_NKT_Cells_Drive-accepted.pdf
DOI : 10.1371/journal.pone.0033413

Éditeur(s) : HAL CCSD Royal Society of Chemistry
Résumé : International audience
Although leishmaniasis has been studied for over a century, the fight against cutaneous, mucocutaneous and visceral forms of the disease remains a hot topic. This review refers to the parasitic cell wall and more particularly to the constitutive glycoconjugates. The structures of the main glycolipids and glycoproteins, which are species-dependent, are described. The focus is on the disturbance of the lipid membrane by existing drugs and possible new ones, in order to develop future therapeutic agents
ISSN: 1477-0520

hal-01174899
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174899
DOI : 10.1039/c5ob00563a
PUBMED : 26130402