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 American Society of Hematology
Résumé : International audience
Zika fever is an Aedes-borne disease caused by a flavivirus (Zika virus, ZIKV, genus Flavivirus). During the past years ZIKV spread in Polynesia, South-America and the Caribbean. Most ZIKV infections are asymptomatic or result in mild febrile disease with rash and conjunctivitis. Attention was recently drawn to non-vectored ZIKV transmission, including sexual, probable blood-borne and mother-to-fetus transmission, and to severe forms such as Guillain-Barré syndrome, acute neurological infections and fetal abnormalities (including microcephaly). Many aspects of Zika fever natural history remain unknown, e.g. the proportion of asymptomatic cases and the duration of viremia. Estimating the prevalence of Zika infections is difficult because a large proportion of infected individuals do not seek medical attention and seroprevalence studies are hampered by antigenic cross-reactivity with other flaviviruses, e.g. dengue virus. Here, we present a study of ZIKV infection in blooddonors from Martinique island (French West Indies, Caribbean region), with novel epidemiological, biological and clinical information that refine the picture of Zika fever in adults.
ISSN: 0006-4971

inserm-01415646
http://www.hal.inserm.fr/inserm-01415646
http://www.hal.inserm.fr/inserm-01415646/document
http://www.hal.inserm.fr/inserm-01415646/file/2016%2C%20Gallian%20et%20al%20-%20Zika%20virus%20in%20asymptomatic%20blood%20donors%2C%20Martinique%20%281%29.pdf
DOI : 10.1182/blood-2016-09-737981

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Toxoplasmosis is a life-threatening infection in immunocompromised patients (ICPs). The definite diagnosis relies on parasite DNA detection, but the incidence and burden of disease are ill-known in HIV-negative patients. A three-year retrospective study was conducted in 15 reference laboratories from the network of the French National Reference Center for Toxoplasmosis, to record the frequency of Toxoplasma DNA detection in ICPs, to review the molecular methods used for diagnosis and the prevention measures implemented in transplant patients. During the study period, out of 31,640 PCR performed in ICPs, 610 were positive (323 patients). Blood (n=337), cerebrospinal fluid (n=101) and aqueous humor (n=100) samples were more frequently positive. Chemoprophylaxis schemes in transplant patients differed between centers. PCR follow-up of allogeneic hematopoietic stem-cell transplant (allo-HSCT) patients was implemented in 8/15 centers. Data from 180 patients (13 centers) were further analyzed regarding clinical setting and outcome. Only 68/180 (38%) patients were HIV+; the remaining 62% consisted in 72 HSCT, 14 solid-organ transplants, and 26 miscellaneous immunodeficiencies. Cerebral toxoplasmosis and disseminated toxoplasmosis were most frequently observed in HIV and transplant patients, respectively. Of 72 allo-HSCT patients with a positive PCR, 23 were asymptomatic; all were diagnosed in centers performing systematic blood PCR follow-up, and received specific treatment. Overall survival of allo-HSCT patients at two months was better in centers with PCR follow-up than in other centers (p<0.01). This study provides updated data on the frequency of toxoplasmosis in HIV-negative ICPs and suggests that regular PCR follow-up of allo-HSCT patients could guide pre-emptive treatment and improve outcome.
ISSN: 0095-1137

hal-01134189
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134189
DOI : 10.1128/JCM.03282-14
PUBMED : 25762774

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) : Edp Sciences S A
Résumé : Reared sea bass were submitted to six stressful situations: hyperoxia with or without hypercapnia, increased stocking density in an open flow or recirculating system, transfer to another tank and nodavirus injection. The potentially negative impact of these factors on the lives of sea bass was investigated by measuring 9 water parameters and 19 fish parameters including total serum protein (TSP). TSP has already been used to evaluate stress. The present study investigates data of previous and new experiments, concentrating on the potential use of TSP as a routine indicator to assess welfare in sea bass reared on fish farms. In the current experiment, oxygen and carbon dioxide were seen to affect levels of TSP, but alterations were too erratic to enable proper comparison, probably because they are normal components of the fish environment and become toxic only by dose increase. TSP decreased when stocking density increased. After transfer to another tank, TSP decreased to 14% for three weeks and then increased during the fourth week through compensative overproduction, before returning to normal levels after 2 months. The results confirmed that transfer is an important stress factor for fish, with cumulative effects for successive transfers. TSP alteration of nodavirus-injected fish depends on the type of symptoms, which can be divided into 3 groups: (i) dying fish, in which TSP increased sharply due to over-production of protein involved in non-specific defences and inflammation, then decreased dramatically before death; (ii) whirling fish, a group that included both fish that later died, in which TSP decreased, and fish that subsequently survived, in which TSP increased due to development of specific immunity; and (iii) asymptomatic fish, in which TPS was similar to control levels and which were probably insensitive to nodavirus and/or had developed defences. In this paper, different mechanisms of TSP alteration are proposed and the interest of TSP as a field parameter is discussed. TSP is a non-destructive parameter that is robust, easy to measure everywhere and cheap, representing a suitable way of monitoring the overall welfare of fish by its regular increase. It can be used only as a "warning" of poor rearing conditions, however, and further investigations would be needed to identify the specific stress or health disorder.
Aquatic Living Resources (0990-7440) (Edp Sciences S A), 2011-04 , Vol. 24 , N. 2 , P. 121-127

Droits : EDP Sciences, IFREMER, IRD 2011
http://archimer.ifremer.fr/doc/00043/15382/12740.pdf
DOI:10.1051/alr/2011130
http://archimer.ifremer.fr/doc/00043/15382/

Éditeur(s) : Elsevier
Résumé : Vibrio tapetis is the marine bacterium responsible for the brown ring disease (BRD) affecting die manila clam, Ruditapes philippinarum. Identification of V tapelis has been previously performed using biochemical criteria and serological procedures. All of these methods are time consuming and ill-adapted to individual screening. This study describes an oligonucleotidic probe (Vt446) and two PCR primers, deduced from the 16S rDNA sequence, allowing a fast and specific V tapetis identification using dot blot hybridisation and species-specific primed PCR (SSP-PCR). The probe and primers have been tested on 60 strains, including referenced Vibrio sp., Gram negative and positive bacteria, marine bacteria samples and isolated clam bacteria. For all the 19 V tapetis strains, the results of PCR assays consistently corroborated those of the agglutination tests. The detection limit was estimated to be 10(2) CFU ml(-1). The SSP-PCR method has resulted in V tapetis detection in larvae, m diseased clams, and in asymptomatic broodstock clams that later developed BRD. In conclusion, the two SSP-PCR primers were useful for direct and fast identification of V tapetis strains isolated in clams, and are well suited for the screening of individual R. philippilnarum broodstock clams and larvae from the hatchery. (C) 2005 Elsevier B.V. All rights reserved.
Aquaculture (0044-8486) (Elsevier), 2006-03 , Vol. 253 , N. 1-4 , P. 25-38

Droits : 2005 Elsevier B.V. All rights reserved
http://archimer.ifremer.fr/doc/2006/publication-1692.pdf
DOI:10.1016/j.aquaculture.2005.03.047
http://archimer.ifremer.fr/doc/00000/1692/

Éditeur(s) : HAL CCSD Centers for Disease Control and Prevention
Résumé : International audience
To assess the prevalence of malaria among illegal gold miners in the ă French Guiana rainforest, we screened 205 miners during May-June 2014. ă Malaria prevalence was 48.3%; 48.5% of cases were asymptomatic. ă Patients reported self-medication with artemisinin-based combination ă therapy. Risk for emergence and spread of artemisinin resistance among ă gold miners in the rainforest is high.
ISSN: 1080-6040

hal-01467560
https://hal.archives-ouvertes.fr/hal-01467560
DOI : 10.3201/eid2205.151957

Éditeur(s) : HAL CCSD
Résumé : International audience
Realized in French Polynesia among 274 patients with elephantiasis, this survey studied the microfilaremia, the eosinophily, the immunoglobulin titers and the antifilarian antibodies (done by passive hemagglutination) for Wuchereria bancrofti var. pacifica. Patients with elephantiasis seldom have circulating microfilariae in their blood. Hypereosinophily is frequent but rarely high. It is similar to the one patients with microfilaremia. There is a trend towards neutropenia during lymphangitic crisis that occur on an elephantiasis limb. The IgE titer is clearly increased, the IgG one is lesser elevated. The mean values are identical to those encoutered among microfilariae asymptomatic cariers. On the other hand the serodiagnosis is more frequently positive among elephantiasic patients.
Bull Soc Pathol Exot Filiales

hal-00715424
https://hal.univ-antilles.fr/hal-00715424
PUBMED : 385164

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART). The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2-4 weeks) initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs. METHODOLOGY/PRINCIPAL FINDINGS: Short term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs. CONCLUSIONS: Our results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.
ISSN: 1932-6203

hal-00876945
https://hal.archives-ouvertes.fr/hal-00876945
https://hal.archives-ouvertes.fr/hal-00876945/document
https://hal.archives-ouvertes.fr/hal-00876945/file/Impactsur Short-Term-accepted.pdf
DOI : 10.1371/journal.pone.0037348

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Cytomegalovirus (CMV) infection is common among HIV-infected patients but its repercussion on the course of CD4+ and CD8+ T cells after cART initiation remains elusive. The French Dat'AIDS cohort enrolled 5,688 patients on first-line cART, from which we selected patients who achieved HIV suppression for at least 12 months without modification of cART, and for whom CMV serostatus was available. Five hundred and three patients fulfilled the selection criteria (74% male, median age 43 yrs, 15.5% CDC stage C), of whom 444 (88.3%) were seropositive for CMV (CMV+). Multivariate analyses using mixed-linear models adjusted for the time from HIV suppression, sex, age, transmission risk group, duration of HIV follow-up, the interaction between time from HIV suppression and CMV+ serol-ogy, and the nadir CD4 count revealed a negative correlation between CMV+ and CD4: CD8 ratio (coeff. =-0.16; p = 0.001). This correlation was also observed among patients displaying optimal CD4 recovery (!500 cells/mm3 at M12; coeff. =-0.24; p = 0.002). Hence, CMV+ serostatus antagonizes normalization of the CD4:CD8 ratio, although further analyses of the impact of co-morbidities that associate with CMV serostatus, like HCV infection, are needed to elucidate this antagonism formally. However, this might reflect a premature T cell senescence, thus advocating for a close monitoring of T cells in CMV co-infected patients. In addition, our results raise the question of the benefit of treatment for asymptomatic CMV co-infection in HIV-infected patients.
ISSN: 1932-6203

inserm-01418700
http://www.hal.inserm.fr/inserm-01418700
http://www.hal.inserm.fr/inserm-01418700/document
http://www.hal.inserm.fr/inserm-01418700/file/journal.pone.0165774.PDF
DOI : 10.1371/journal.pone.0165774

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
ABSTRACT: Eclipsed by the debates about malaria incidence and severity in individual patients, malaria transmission in helminth-infected persons has so far received very little attention. Studies in humans have shown increased malaria incidence and prevalence, and a trend for a reduction of symptoms in patients with malaria. This suggests that such patients could possibly be less likely to seek treatment thus carrying malaria parasites and their gametocytes for longer durations, therefore, being a greater potential source of transmission. In addition, in humans, a study showed increased gametocyte carriage, and in an animal model of helminth-malaria co-infection, there was increased malaria transmission. These elements converge towards the hypothesis that patients co-infected with worms and malaria may represent a hub of malaria transmission. The test of this hypothesis requires verifying, in different epidemiological settings, that helminth-infected patients have more gametocytes, that they have less symptomatic malaria and longer-lasting infections, and that they are more attractive for the vectors. The negative outcome in one setting of one of the above aspects does not necessarily mean that the other two aspects may suffice to increase transmission. If it is verified that patients co-infected by worms and malaria could be a transmission hub, this would be an interesting piece of strategic information in the context of the spread of anti-malarial resistance and the malaria eradication attempts.
ISSN: 1475-2875

inserm-00758017
http://www.hal.inserm.fr/inserm-00758017
http://www.hal.inserm.fr/inserm-00758017/document
http://www.hal.inserm.fr/inserm-00758017/file/1475-2875-11-376.pdf
DOI : 10.1186/1475-2875-11-376

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BackgroundMalaria is endemic in French Guiana, an overseas territory of France on the Guiana Shield. Since 2005, notified malaria cases are decreasing. However, new data show that malaria affects many Brazilian gold miners working illegally in French Guiana, the majority of whom are not counted in official data. In addition, one major concern is the usual practice of improper self-treatment in this mining population, raising fear of the development of antimalarial resistance. This prospective study, conducted in 2015, aimed to estimate the prevalence of Plasmodium spp. in illegal gold miners working in French Guiana. MethodsThe recruitment of gold miners was carried out in resting sites along the French Guiana-Suriname border, where they go for supplies, medical care or leisure. After recording agreement, three malaria diagnostic methods were performed: rapid diagnostic test, microscopy and PCR,ResultsAmong 421 persons recruited in the study, malaria prevalence, detected by nested-PCR, was 22.3% (CI=[18.3-26.3], n=94/421) of which 84% were asymptomatic. ConclusionThis significant malaria reservoir in a mobile and illegal population with difficult access to a health care system raises the threat of artemisinin resistance and puts the population of the Guiana Shield at risk of new transmission foci while countries of the region aim at malaria elimination. Even though French legislation may hamper dealing with this population, France must face the reality of malaria in illegal gold miners in order to meet its commitment to malaria elimination.
ISSN: 1475-2875

hal-01346800
https://hal.archives-ouvertes.fr/hal-01346800
https://hal.archives-ouvertes.fr/hal-01346800/document
https://hal.archives-ouvertes.fr/hal-01346800/file/2016%2C%20Douine%20-%20Prevalence%20of%20Plasmodium%20spp.%20in%20illegal%20gold%20miners%20in%20French%20Guiana%20in%202015.pdf
DOI : 10.1186/s12936-016-1367-6

Éditeur(s) : HAL CCSD Centers for Disease Control and Prevention
Résumé : International audience
To assess the prevalence of malaria among illegal gold miners in the French Guiana rainforest, we screened 205 miners during May-June 2014. Malaria prevalence was 48.3%; 48.5% of cases were asymptomatic. Patients reported self-medication with artemisinin-based combination therapy. Risk for emergence and spread of artemisinin resistance among gold miners in the rainforest is high.
ISSN: 1080-6040

Droits : http://creativecommons.org/licenses/by/
pasteur-01305106
https://hal-pasteur.archives-ouvertes.fr/pasteur-01305106
https://hal-pasteur.archives-ouvertes.fr/pasteur-01305106/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01305106/file/15-1957.pdf
DOI : 10.3201/eid2205.151957.

Éditeur(s) : HAL CCSD Elsevier
Résumé : Field isolates of Toxoplasma gondii in Europe and North America have been grouped into three clonal lineages that display different virulence in mice. Whether the genetic structure of the parasite is related to clinical expression in humans has not yet been demonstrated. We developed an enzyme-linked immunosorbent assay which uses lineage-specific, polymorphic polypeptides derived from the dense granule antigens, GRA5 and GRA6. Our goal was to compare serotypical patterns observed in asymptomatic versus symptomatic (ocular disease and severe infection in human immunodeficiency virus (HIV)-positive patients) infections among patients from Europe and South America. Independent of the clinical presentation of the disease, serotypes differed according to geographical origin, with a homogeneous distribution of serotype II in Europe and of serotypes I and III in South America. We conclude that GRA5-GRA6 serotyping is an interesting tool to study serotype prevalence in populations but it is not an accurate marker of pathogenicity of Toxoplasma infection in humans.
ISSN: 1286-4579

hal-00306841
https://hal.archives-ouvertes.fr/hal-00306841
DOI : 10.1016/j.micinf.2008.04.001
PUBMED : 18539501

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Varicella zoster virus (VZV) is a leading cause of acute viral encephalitis but little is known about its clinical, biological and imaging features. Furthermore, the most favourable treatment regimen has not been determined. We studied a prospective cohort of 20 HIV-negative patients presenting with acute VZV encephalitis caused by primary infection or reactivation. VZV was identified in 16 of 20 cases by PCR detection of the DNA in the cerebrospinal fluid. The four remaining cases occurred during or soon after a VZV rash. The median age of the 17 adults was 76 (19-86) years; the three other patients were children (0.5-5 years). Three patients were immunocompromised. Nine adult patients presented with a rash. Eighteen patients presented with fever and an acute encephalitic syndrome: diffuse brain dysfunction, focal neurological signs, seizures and cranial nerve palsies. Three patients presented with either ventricular or subdural haemorrhage, one with myelitis, and one with asymptomatic stenosis of the middle cerebral artery. The imaging was either normal or revealed non-specific abnormalities such as cortical atrophy but no evidence of stroke. All patients were given acyclovir at various dosages and durations but the case fatality rate remained high (15%) and sequelae were frequently observed either at discharge or at follow-up 3 years later.
ISSN: 1198-743X

hal-00875232
https://hal.archives-ouvertes.fr/hal-00875232
PUBMED : 22085160
DOI : 10.1111/j.1469-0691.2011.03705.x

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