Éditeur(s) : HAL CCSD
Résumé : International audience
Objective To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. Methods Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. Results The study population included 157 patients (mean age 49.4 ± 14.1), with a follow-up of 7.4 ± 6.4 years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p = 0.005) and with the presence of ANCA (p < 0.001). Overall, 59% of patients had polyangiitis as defined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifestations including arthralgias (p = 0.02) and renal disease (p = 0.024), had higher peripheral eosinophilia (p = 0.027), and a trend towards less myocarditis (p = 0.057). Using predefined criteria of vasculitis and surrogates of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features. Conclusion We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as hypereosinophilic asthma with systemic (non vasculitic) manifestations. © 2016 Elsevier B.V.
Autoimmunity Reviews

hal-01467544
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467544
DOI : 10.1016/j.autrev.2016.09.018
PUBMED : 27671089

Éditeur(s) : Actes de Colloque: Avancées et nouvellles technologies en toxinologie, éditeurs: Julien BARBIER, Evelyne BENOIT, Pascale MARCHOT, César MATTEI, Denis SERVENT
Résumé : Over the past seven years, methods available for the detection of phycotoxins have been extensively reviewed in a number of international expert committees, such as the consultations organised by FAO/IOC/WHO and EFSA, as well as by individual scientists. These reviews have shown that the methods available have severe limitations for the use in official control, either due to their limited scope and detection capability or due to a lack of calibration standards, reference materials and validation efforts. The present review focuses on recent developments in the detection of phycotoxins in several areas of applied research. Not being able to exhaustively describe all recent developments, the review focussed on three areas of interest to the authors: (i) detection of ultra-trace amounts of toxins, (ii) metabolism of toxins and their localisation in biological tissues, and (iii) approaches to detect unknown toxins or analogues of known toxins. Miniaturisation in combination with physico-chemical techniques appears to be a very efficient approach to detect low trace amounts of individual toxin analogues. In particular, the detection of azaspiracids and okadaic acid and analogues, using micro-filtration and on-line pre-concentration techniques, has shown to be useful for the characterisation of various algal and shellfish species. In the area of interactions of toxins with shellfish and mammalian systems, it is noted that several studies on biomarkers reveal either protein biomarkers of exposure to toxins or potential pathways of metabolism of the toxins themselves. A particular focus is given to recent findings in the areas of brevetoxin metabolism and biomarkers as well as azaspiracid localisation and metabolism. Finally, the detection of novel compounds is a particularly challenging area. The interest in this area has risen over the past years following cases of unexplained mouse toxicity such as the UK cockle toxicity and the French atypical toxicity in mussels and oysters from the Atlantic and Mediterranean coasts. Some attention is given to immuno-, functional and cellular bio-assays for the identification of bioactive agents in shellfish.
Durant les sept dernières années, les méthodes disponibles pour la détection des phycotoxines ont été abondamment revues dans de nombreux groupes internationaux d’expertises, tels que les consultations organisées par FAO/IOC/WHO et EFSA ainsi que dans de nombreux articles scientifiques de synthèse. Ces revues ont démontré que, vis-à-vis des systèmes de régulations officiels, les méthodes disponibles présentent des limites d’utilisation importantes. Soit elles ont un périmètre réduit et des limites de détection trop élevées, soit il y a un manque d’étalons, de matériaux de référence ou d’efforts de validation. La présente revue focalise sur les développements récents dans la détection de phycotoxines en recherche appliquée. Sans vouloir décrire de manière exhaustive tous les développements récents, la revue examine trois domaines d’intérêt pour les auteurs : (i) la détection de quantités ultra-traces de toxines, (ii) la métabolisation et la localisation des toxines dans des tissus biologiques, et (iii) les approches pour la détection de toxines non-répertoriées ou des analogues de toxines connues. La miniaturisation en combinaison avec les techniques physico-chimiques constitue apparemment une approche efficace pour la détection de faibles traces d’analogues individuels des toxines. En particulier, la micro-filtration et des techniques de pré-concentration en ligne se sont montrées utiles pour la détection des azaspiracides et des toxines du groupe de l’acide okadaïque dans la caractérisation de diverses espèces d’algues et de coquillages. Dans le domaine des interactions des toxines avec les coquillages et des systèmes vivants de mammifères, nous avons noté que plusieurs études sur les bio-marqueurs révèlent soit des marqueurs protéiniques d’exposition aux toxines, soit des marqueurs du métabolisme des toxines elles-mêmes. Un intérêt spécifique a été trouvé dans les résultats d’étude sur le métabolisme des brévétoxines et des azaspiracides. La détection des composés bioactifs non-répertoriés constitue un défi particulièrement difficile. Ce domaine a trouvé plus d’intérêt dû à plusieurs cas de toxicités inexpliquées dans le test souris telles que les toxicités observées dans les coques en provenance de Grande-Bretagne ou encore dans les moules et huîtres des côtes méditerranéennes et atlantiques françaises. Une attention particulière a été consacrée à l’identification d’agents bioactifs par les essais cellulaires ou fonctionnels ou basés sur la détection immuno-chimique.

Droits : 2010 SFET
http://archimer.ifremer.fr/doc/00019/12975/9949.pdf
http://archimer.ifremer.fr/doc/00019/12975/

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
The immune system contributes to maintaining the integrity of the organism. It can be the target of many xenobiotics, and immunotoxicology attempts to analyze the immunological alterations caused by exposure to these xenobiotics. Several environmental pollutants are strongly suspected of acting on the immune system to cause a decrease in the organism protective functions. Thus, polycyclic aromatic hydrocarbons, well known for their carcinogenic effects, have also been shown to induce immunosuppressive effects, pro-inflammatory actions and some hypersensitivity reactions, involved in the development of various pathologies. These different immunotoxic effects have mainly been identified by experimental studies on animals and our knowledge of the effects on humans remains incomplete. To better understand the immunotoxic effects of exposure to environmental pollutants and their consequences for human health, it is appropriate to strengthen immunotoxicology studies on humans.
Le système immunitaire contribue à la surveillance et au maintien de l’intégrité de l’organisme. Il peut être la cible de nombreux xénobiotiques, et l’immunotoxicologie s’attache à étudier les différentes atteintes immunologiques induites par l’exposition à ces xénobiotiques. De nombreux polluants environnementaux sont fortement suspectés d’agir sur le système immunitaire pour entraîner une diminution des fonctions de protection de l’organisme. Ainsi, les hydrocarbures aromatiques polycycliques, bien connus pour leurs effets cancérogènes, se sont révélés également capables d’induire des effets immunosuppresseurs, d’entraîner des actions pro-inflammatoires et de majorer certaines réactions d’hypersensibilité, impliqués dans le développement de diverses pathologies. Ces différents effets immunotoxiques ont surtout été identifiés par des études expérimentales chez l’animal et la transposition de ces effets à l’homme reste incomplète. Pour mieux appréhender les effets immunotoxiques de l’exposition aux polluants environnementaux et leurs conséquences sur la santé humaine, il convient donc de renforcer les études en immunotoxicologie chez l’homme.
ISSN: 1775-8785

hal-01467562
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467562
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467562/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467562/file/Effets%20immunotoxiques%20des%20polluants%20environnementaux_accepted.pdf
DOI : 10.1016/j.admp.2016.09.003

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 Impact journals
Résumé : International audience
Interleukin (IL)-33 has been recently reported to be strongly pro-fibrogenic in various models of liver disease. Our aim was to study the role of endogenous IL-33 in a diet-induced model of steatohepatitis. IL-33 deficient mice and wild type (WT) littermates received a high-fat diet (HFD), or a standard diet for 12 weeks. The HFD-induced steatohepatitis was associated with an upregulation of IL-33 transcripts and protein. An insulin tolerance test revealed lower systemic insulin sensitivity in IL33-/-HFD mice than in WT-HFD mice. Nevertheless, IL-33 deficiency did not affect the severity of liver inflammation by histological and transcriptomic analyses, nor the quantity of liver fibrosis. Livers from HFD mice had more myeloid populations, markedly fewer NKT cells and higher proportion of ST2+ Treg cells and ST2+ type 2 innate lymphoid cells (ILC2), all unaffected by IL-33 deficiency. In conclusion, deficiency of endogenous IL-33 does not affect the evolution of experimental diet-induced steatohepatitis towards liver fibrosis.
ISSN: 1949-2553

hal-01578584
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578584
DOI : 10.18632/oncotarget.18335
PUBMED : 28611297

Éditeur(s) : Université de Montpellier II
Résumé : The sea bass, Dicentrarchus labrax, has been subjected to intensive aquaculture on the Mediterranean cost for ten years. Marine fish hatcheries are key factors in the aquaculture field, and face different pathologies, especially one of viral origin (nodavirus) that could challenge their feasibility. Consequently, we have tried to provide some data on larvae and spawning stocks. Firstly, we have studied the immunoglobulins, components of the specific humoral immunity, and their role as antibodies. On adult basses, these immunoglobulins are tetrameric molecules with high molecular weight (850 kD), made of heavy (H) - 80 kD and light (L) - 26 kD chains. In the eggs, simplest forms such as monomeric or dimeric are brought to the fore; they are located under the chorionic membrane. Secondly, we have studied the development of the immunity system on larvae, preparing IgM assays with ELISA method, the study on the organogenesis of the main lymphoid organs, and using flow cytometry for the ontogenesis of IgM producing cell. Based on this experience, we can propose a date for the immunocompetence onset of the bar, i.e. from the 54th day of the hatchery phase. Finally, we made the most of these different results to study a viral pathology (nodavirus) in spawners and larvae. We defined an experimental contamination model for larvae and eggs, and we highlighted that eggs born from vaccinated hen fishes were protected against the nodavirus.
Le bar, Dicentrarchus labrax, fait l'objet d'une aquaculture intensive sur le littoral Méditerranéen depuis une dizaine d'années. Les écloseries marines représentent un des maillons clefs de cette filière aquacole, et sont confrontées à différentes pathologies, dont une d'origine virale (nodavirus), pouvant remettre en cause leur faisabilité. Aussi, nous avons tenté d'apporter quelques données concernant la protection des larves et des géniteurs reproducteurs. Dans un premier temps, nous avons étudié les immunoglobulines, éléments de l'immunité spécifique humorale ainsi que leur rôle anticorps. Chez les bars adultes ces immunoglobulines sont des molécules tétramériques de haut poids moléculaire (850 kD), composées de chaînes lourdes (H) de 80 kD et légères (L) de 26 kD. Dans les oeufs, des formes plus simples, monomériques ou dimériques, sont mises en évidence et sont localisées sous la membrane chorionique. Dans un second temps, nous avons étudié la mise en place du système immunitaire spécifique chez les larves, en effectuant le dosage des IgM par ELISA, l'étude de l'organogenèse des principaux organes lymphoïdes, puis celle de l'ontogenèse des cellules productrices d'IgM par cytométrie de flux. L'ensemble de cette étude nous permet de proposer une date d'acquisition de l'immunocompétence à partir du 54ème jour d'élevage chez le bar. Enfin, ces différents résultats ont été mis à profit dans le cadre d'une pathologie virale (nodavirus) touchant les reproducteurs et les larves. Après avoir défini un modèle de contamination expérimental des larves et des oeufs, nous avons mis en évidence une protection des oeufs lorsque ceux-ci proviennent d'une femelle vaccinée (vaccin expérimental) contre le nodavirus.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1997/these-1265.pdf
http://archimer.ifremer.fr/doc/00000/1265/

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
'Alarmins' are a group of proteins or molecules that are released from cells during cellular demise to alert the host immune system. Two of them, Interleukin-33 (IL-33) and high-mobility group box-1 (HMGB1), share many similarities of cellular localization, functions and involvement in various inflammatory pathologies including hepatitis. The expressions of IL-33 and HMGB1, and their receptors ST2 and receptor for advanced glycation end products (RAGE), are substantially up-regulated during acute and chronic hepatitis. Recent data evidence a possible protective role of IL-33/ST2 axis during liver injury. A contrast in expression of IL-33 and HMGB1 alarmins were associated with type of hepatocellular death mediated by immune cells or hepato-toxic agents. The massive release of active form of IL-33 from hepatocytes may affect the recruitment and activation of its ST2-positive target immune cells in the liver to confer its alarmin functions. This review highlights the emerging roles of alarmin proteins in various liver pathologies, by focusing on classical HMGB1 and a newly discovered alarmin, the IL-33.
ISSN: 1478-3223

hal-00874209
https://hal.archives-ouvertes.fr/hal-00874209
DOI : 10.1111/j.1478-3231.2012.02802.x
PUBMED : 22530772

Éditeur(s) : Elsevier
Résumé : injection of non-specific dsRNA initiates a broad-spectrum innate antiviral immune response in the Pacific white shrimp, Litopenaeus vannamei, however, the receptor involved in recognition of this by-product of viral infections remains unknown. In vertebrates, dsRNA sensing is mediated by a class of Toll-like receptors (TLRs) and results in activation of the interferon system. Because a TLR (lToll) was recently characterized in L. vannamei, we investigated its potential role in dsRNA recognition. We showed that injection of non-specific RNA duplexes did not modify lToll gene expression. A reverse genetic approach was therefore implemented to study its role in vivo. Silencing of lToll did not impair the ability of nonspecific dsRNA to trigger protection from white spot syndrome virus and did not increase the shrimp susceptibility to viral infection, when compared to controls. In contrast, gene-specific dsRNA injected to specifically silence lToll expression activated an antiviral response. These data strongly suggest that shrimp lToll plays no role in dsRNA-induced antiviral immunity. (C) 2009 Elsevier Ltd. All rights reserved.
Developmental & Comparative Immunology (0145-305X) (Elsevier), 2009-07 , Vol. 33 , N. 7 , P. 806-810

Droits : 2009 Elsevier Ltd All rights reserved.
http://archimer.ifremer.fr/doc/2009/publication-6428.pdf
DOI:10.1016/j.dci.2009.02.005
http://archimer.ifremer.fr/doc/00000/6428/

Éditeur(s) : HAL CCSD
Résumé : Due to their phylogenetic position outside from Bilateria, cnidarians and ctenophores are key phyla to understanding the origin and early evolution of molecular mechanisms, cell types, or body plan features at the level of Metazoa. Unlike other non-bilaterian phyla (sponges and placozoans), they possess neurons and muscle cells. The first part of my work relates to the problem of the origin of the metazoan nervous system. Recent studies have suggested a dual origin for nerve cells, with ctenophore neurons having emerged independently from those of cnidarians and bilaterians. This hypothesis relies on phylogenomic analyses supporting ctenophores as sister-group to all other metazoans, and on the purported absence in ctenophores of almost all well-known neuro-transmission systems, including the cholinergic system. Refuting this claim, I present substantial evidence in favour of acetylcholine (Ach) being used in the ctenophore Pleurobrachia pileus as an extra-cellular messenger, including within the nervous system. This conclusion arises from the conjunction of multiple approaches at the molecular scale (orthology analyses, Ach immuno-localisation, gene in situ hybridisation), at the cellular scale (calcium imaging on muscle cells exposed to Ach) and at the organism scale (pharmacological treatments with an Ach analogue and Ach antagonists). In the second part of my thesis, I address the conservation of molecular mechanisms involved in the control of cellular proliferation. Notably, the Hippo pathway is known for its role in bilaterians in the negative control of cellular proliferation. I show that components of this pathway are conserved in Pleurobrachia pileus and in Clytia hemisphaerica and that the nuclear vs. cytoplasmic localisation of the transcriptional co-factor Yorkie is correlated to the extent of proliferation within C. hemisphaerica tissues. Finally, RNAseq differential gene expression analyses along a cellular conveyor belt of the C. hemisphaerica medusa suggests a tendency for conservation of function among a set of genes whose mammalian orthologues have documented roles in the arrest of cellular proliferation.
Les Cnidaires et les Cténaires sont deux embranchements extérieurs aux Bilatériens qui, de par leur position phylogénétique, constituent des modèles d'étude cruciaux pour comprendre l'origine et l'évolution de mécanismes moléculaires ou encore de types cellulaires à grande échelle chez les Métazoaires. Ils sont les deux seuls embranchements non-Bilatériens à posséder des cellules nerveuses ainsi que des cellules musculaires. La première partie de mon travail de thèse s'inscrit dans le contexte de la compréhension de l'origine du système nerveux des Métazoaires. Des études récentes suggèrent une origine double du système nerveux ; ainsi celui des Cténaires aurait été acquis de manière convergente par rapport à celui des Cnidaires et des Bilatériens. Cela repose sur des données récentes de phylogénomique proposant les Cténaires en tant que groupe-frère de tous les autres Métazoaires et sur l'absence supposée chez les Cténaires de quasiment tous les systèmes de neurotransmission connus y compris le système cholinergique. A l'encontre de ces hypothèses, j'ai pu mettre en évidence l'existence d'un système cholinergique chez le Cténaire Pleurobrachia pileus ainsi que son étroite association avec le système nerveux. Cette conclusion repose sur une multiplicité d'approches à l'échelle moléculaire (analyses d'orthologie, immunolocalisation, hybridations in situ), cellulaire (imagerie calcique) et de l'organisme (approche pharmacologique). Dans la seconde partie de ma thèse, j'aborde la question de la conservation des mécanismes moléculaires impliqués dans le contrôle de la prolifération cellulaire à l'échelle des Métazoaires. J'ai pu mettre en évidence la conservation des acteurs.
https://tel.archives-ouvertes.fr/tel-01633223

NNT : 2015PA066629
tel-01633223
https://tel.archives-ouvertes.fr/tel-01633223
https://tel.archives-ouvertes.fr/tel-01633223v2/document
https://tel.archives-ouvertes.fr/tel-01633223/file/2015PA066629.pdf

Éditeur(s) : Elsevier
Résumé : Antimicrobial peptides play a major role in innate immunity. The penaeidins, initially characterized from the shrimp Litopenaeus vannamei, are a family of antimicrobial peptides that appear to be expressed in all penaeid shrimps. As of recent, a large number of penaeid nucleotide sequences have been identified from a variety of penaeid shrimp species and these sequences currently reside in several databases under unique identifiers with no nomenclatural continuity. To facilitate research in this field and avoid potential confusion due to a diverse number of nomenclatural designations, we have made a systematic effort to collect, analyse, and classify all the penaeidin sequences available in every database. We have identified a common penaeidin signature and subsequently established a classification based on amino acid sequences. In order to clarify the naming process, we have introduced a 'penaeidin nomenclature' that can be applied to all extant and future penaeidins. A specialized database, PenBase, which is freely available at http://www.penbase.immunaqua.com, has been developed for the penaeidin family of antimicrobial peptides, to provide comprehensive information about their properties, diversity and nomenclature. (c) 2005 Elsevier Ltd. All rights reserved.
Developmental & Comparative Immunology (0145-305X) (Elsevier), 2006 , Vol. 30 , N. 3 , P. 283-288

Droits : 2005 Elsevier Ltd All rights reserved
http://archimer.ifremer.fr/doc/2006/publication-2332.pdf
DOI:10.1016/j.dci.2005.04.003
http://archimer.ifremer.fr/doc/00000/2332/

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Environmental exposures, including dietary contaminants, may influence the developing immune system. This study assesses the association between maternal pre-parturition consumption of seafood and wheeze, eczema, and food allergy in preschool children. Fish and shellfish were studied separately as they differ according to their levels of omega-3 polyunsaturated fatty acids (which have anti-allergic properties) and their levels of contaminants. METHODS: The PELAGIE cohort included 3421 women recruited at the beginning of pregnancy. Maternal fish and shellfish intake was measured at inclusion by a food frequency questionnaire. Wheeze, eczema, and food allergy were evaluated by a questionnaire completed by the mother when the child was 2 years old (n = 1500). Examination of the associations between seafood intake and outcomes took major confounders into account. Complementary sensitivity analyses with multiple imputation enabled us to handle missing data, due mostly to attrition. RESULTS: Moderate maternal pre-parturition fish intake (1 to 4 times a month) was, at borderline significance, associated with a lower risk of wheeze (adjusted OR = 0.69 (0.45-1.05)) before age 2, compared with low intake (< once/month). This result was not, however, consistent: after multiple imputation, the adjusted OR was 0.86 (0.63-1.17). Shellfish intake at least once a month was associated with a higher risk of food allergy before age 2 (adjusted OR = 1.62 (1.11-2.37)) compared to low or no intake (< once/month). Multiple imputation confirmed this association (adjusted OR = 1.52 (1.05-2.21)). CONCLUSIONS: This study suggests that maternal pre-parturition shellfish consumption may increase the risk of food allergy. Further large-scale epidemiologic studies are needed to corroborate these results, identify the contaminants or components of shellfish responsible for the effects observed, determine the persistence of the associations seen at age 2, and investigate potential associations with health effects observable at later ages, such as allergic asthma.
ISSN: 1476-069X

Droits : info:eu-repo/semantics/OpenAccess
inserm-00926282
http://www.hal.inserm.fr/inserm-00926282
http://www.hal.inserm.fr/inserm-00926282/document
http://www.hal.inserm.fr/inserm-00926282/file/1476-069X-12-102.pdf
DOI : 10.1186/1476-069X-12-102

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVES: The time from the prenatal period through early childhood is an important window of vulnerability for the developing immune and respiratory systems, both sensitive to environmental chemicals such as solvents. This study sought to examine the effects of solvent exposure during the prenatal and postnatal periods on wheezing, eczema and food allergies in early childhood. METHODS: This study, based on the PELAGIE cohort, included 1505 mother-child pairs with measurements of prenatal and postnatal solvent exposures and data on wheezing, eczema or food allergies. The maternal occupation reported at inclusion, in early pregnancy allowed us to define prenatal occupational solvent exposure (by three specific job-exposure matrices). Data on prenatal and postnatal domestic solvent exposure, that is exposure to products that contain solvents, were obtained from self-administered questionnaires, once at inclusion and again when the child was 2 years old. Outcome data was collected at the 2-year follow-up. Associations between exposures and outcomes were estimated by logistic regression models, after adjustment for potential confounders. RESULTS: No association was observed between prenatal exposure to solvents and the outcomes studied. Postnatal exposure was associated with an increased risk of wheezing (OR=1.80 (95% CI 1.25 to 2.59)) which persisted after adjustment for prenatal exposure. No significant association was observed with eczema or food allergies. CONCLUSIONS: Postnatal exposure to solvent-containing products in the home may increase the risk of wheezing in early childhood. Follow-up studies are needed to determine if the health effects observed at age 2 persist at later ages.
ISSN: 1351-0711

hal-01063913
https://hal.archives-ouvertes.fr/hal-01063913
DOI : 10.1136/oemed-2013-102036
PUBMED : 24996679

Résumé : By looking at the common thread between 4 programs* in which the IFREMER Palavas (34, Languedoc-Roussillon region in France) station took part, this report show the evolution over 20 years in the perception of the pathology of farmed fish, and of the sea bass in particular (Dicentrarchus labrax). During the 1990’s farming techniques became sufficiently reliable to enable to distinguish between problems of a zootechnical nature and those with a pathological origin. In anticipation of future illnesses, the necessary tools and monitoring were implemented in order to study the immune system of the sea bass. These methods arose from the recent creation of anti-immunoglobin monoclonal probes in the sea bass. These techniques, together with others, served to search for a solution to the nodavirus epidemic which struck in1996. In the absence of a cure for this virus, the research focused on knowledge of the virus, its epidemiology and vaccine development. Despite interesting scientific results, the solution withheld to curb the Nodavirus epidemic was zootechnical. This pragmatic outcome catalysed reflections on the role of pathology, leading to notions of health, animal well-being and image. Management choices in the health of farmed fish stocks became a parameter, amongst others, included in a global commercial and farming policy. * Définition des critères d’évaluation de l’immunocompétente chez le loup et le turbot. UMR1 Université Montpellier II IFREMER ; Nodavirus disease of cultured marine fish in Europe. FAIR PL98 4036 EU; Recherche de moyens de dépistage et prévention de la nodavirose du bar. ANVAR 9804041J ; Welfare and Health in Sustainable Aquaculture WEALTH. E.U N°501984.
En prenant comme fil conducteur les travaux de 4 programmes* auxquels a participé la station IFREMER de Palavas (34), ce rapport montre l’évolution sur 20 ans de la perception de la pathologie des poissons d’élevages et du loup en particulier (Dicentrarchus labrax). Dans les années 1990 les techniques d’élevages devinrent suffisamment fiables pour permettre de distinguer les problèmes d’origines zootechniques de ceux d’origines pathologiques. En prévision des futures maladies potentielles, les outils d’étude et de suivi du système immunitaire spécifique du loup furent mis en place. Ils découlaient de la création récente de sondes monoclonales anti-immunoglobulines de loup. Ces techniques, couplées à d’autres, servirent à chercher une solution à l’épidémie de nodavirose des années 1996. En l’absence de traitement pour un virus l’accent fut mis sur la connaissance du virus, de son épidémiologie et de la vaccination. Bien que les résultats scientifiques furent très satisfaisants la solution trouvée pour juguler l’épidémie de Nodavirose fut zootechnique. Cette issue pragmatique catalysa une réflexion sur le rôle de la pathologie qui maturait depuis plusieurs années et qui déboucha sur la notion de santé, de bien être des animaux et d’image. Les choix de gestion de la santé des cheptels devinrent un paramètre, parmi d’autres, s’incluant dans d’une politique globale d’élevage et commerciale * Définition des critères d’évaluation de l’immunocompétente chez le loup et le turbot. UMR1 Université Montpellier II IFREMER ; Nodavirus disease of cultured marine fish in Europe. FAIR PL98 4036 EU; Recherche de moyens de dépistage et prévention de la nodavirose du bar. ANVAR 9804041J ; Welfare and Health in Sustainable Aquaculture WEALTH. E.U N°501984.

Droits : 2013 Ifremer
http://archimer.ifremer.fr/doc/00167/27866/26103.pdf
http://archimer.ifremer.fr/doc/00167/27866/26105.pdf
http://archimer.ifremer.fr/doc/00167/27866/26106.pdf
http://archimer.ifremer.fr/doc/00167/27866/

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Persistent organic pollutants may affect the immune and respiratory systems, but available evidence is based on small study populations. We studied the association between prenatal exposure to dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyl 153 (PCB 153) and children's respiratory health in European birth cohorts. METHODS: We included 4608 mothers and children enrolled in 10 birth cohort studies from 7 European countries. Outcomes were parent-reported bronchitis and wheeze in the first 4 years of life. For each cohort, we performed Poisson regression analyses, modeling occurrences of the outcomes on the estimates of cord-serum concentrations of PCB 153 and DDE as continuous variables (per doubling exposure) and as cohort-specific tertiles. Summary estimates were obtained through random-effects meta-analyses. RESULTS: The risk of bronchitis or wheeze (combined variable) assessed before 18 months of age increased with increasing DDE exposure (relative risk [RR] per doubling exposure = 1.03 [95% confidence interval = 1.00-1.07]). When these outcomes were analyzed separately, associations appeared stronger for bronchitis. We also found an association between increasing PCB 153 exposure and bronchitis in this period (RR per doubling exposure = 1.06 [1.01-1.12]) but not between PCB 153 and wheeze. No associations were found between either DDE or PCB 153 and ever-wheeze assessed after 18 months. Inclusion of both compounds in the models attenuated risk estimates for PCB 153 tertiles of exposure, whereas DDE associations were more robust. CONCLUSION: This large meta-analysis suggests that prenatal DDE exposure may be associated with respiratory health symptoms in young children (below 18 months), whereas prenatal PCB 153 levels were not associated with such symptoms.
Epidemiology (Cambridge, Mass.)

hal-01063930
https://hal.archives-ouvertes.fr/hal-01063930
DOI : 10.1097/EDE.0000000000000097
PUBMED : 24776790

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : International audience
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells, which promote inflammation and induce hepatocyte death, mediated by the activated invariant natural killer T (iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs, such as the spleen, thymus, and bone marrow in Parp2-deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis. We show that 1) the genetic inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without deregulating cytokine expression and leucocyte recruitment; 2) cellularity was lower in the thymus, but not in spleen, liver, or bone marrow of Parp2-/- mice; 3) spleen and liver iNKT lymphocytes, as well as thymic T and NKT lymphocytes were reduced in Parp2 knockout mice. In conclusion, our results suggest that the defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver damage, thus protecting the mice from hepatitis.NEW & NOTEWORTHY The genetic inactivation of Parp2, but not Parp1, protects mice from concanavalin A hepatitis. Immune cell populations are lower in the thymus, but not in the spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as thymic T and NKT lymphocytes, are reduced in Parp2-deficient mice
ISSN: 0193-1857

hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/file/102513_1_merged_1499199857-1.pdf
DOI : 10.1152/ajpgi.00436.2016

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

Résumé : La conchyliculture connaît depuis une trentaine d'années une progression régulière de ses productions à travers le monde. Elle représente une activité économique importante avec plus de 240 000 tonnes de coquillage produit annuellement en France. Cependant le développement de cette activité peut être limité par des mortalités parfois massives dues à des maladies infectieuses. L'augmentation des productions peut être expliquée par l'amélioration des méthodes d'élevage grâce à une meilleure connaissance de la biologie des bivalves et des processus physiologiques liés à leur reproduction : l'apparition de l'élevage larvaire en écloserie a permis de pallier le caractère aléatoire et souvent insuffisant du captage naturel. Ces nouvelles techniques ont permis d'acquérir une certaine indépendance vis-à-vis des pontes naturelles, mais ont entraîné une augmentation des transferts d'animaux entre les bassins conchylicoles, une augmentation des densités de mollusques et le développement d'une espèce cible par bassin. Ces actions ont contribué à l'apparition et à la dissémination de nouvelles maladies entraînant de très fortes pertes pour la conchyliculture. De plus, la palourde, comme tous les mollusques marins, présente des caractéristiques biologiques qui laissent peu de possibilités d'actions pour protéger une production vis-à-vis de maladies infectieuses: la culture de ces espèces en milieu ouvert rend tout traitement impossible du fait des quantités de substance à utiliser, et de la forte probabilité de contamination des animaux. Cette méthode peut être appliquée dans le cas d'élevages intensifs : écloseries, nurseries. Le système immunitaire des mollusques est primitif, ils ne possèdent pas de lymphocytes B et lymphocytes T, ce qui empêche toute réponse immune spécifique et rend la vaccination impossible. L'absence d'anticorps spécifique complique la recherche d'agent pathogène, celle-ci n'est possible que par un diagnostic direct, essentiellement réalisé grâce à l'histologie ou à la microscopie.

Droits : 2006 IUT La Rochelle, Ifremer
http://archimer.ifremer.fr/doc/00033/14457/11759.pdf
http://archimer.ifremer.fr/doc/00033/14457/

Éditeur(s) : HAL CCSD Federation of American Society of Experimental Biology
Résumé : International audience
The innate immune system is able to detect bacterial LPS through the pattern recognition receptor CD14, which delivers LPS to various TLR signaling complexes that subsequently induce intracellular proinflammatory signaling cascades. In a previous study, we showed the overproduction of the soluble form of CD14 (sCD14) by macrophages from patients with cystic fibrosis (CF). CF is an autosomal recessive disorder that is caused by mutations in the gene that encodes the CFTR protein and is characterized by persistent inflammation. Macrophages play a significant role in the initial stages of this disease due to their inability to act as suppressor cells, leading to chronic inflammation in CF. In this work, we investigated the origin of sCD14 by human macrophages and studied the effect of sCD14 on the production of inflammatory cytokine/chemokine. Our data indicate that sCD14 stimulate proinflammatory cytokine/chemokine production in a manner that is independent of LPS but dependent on the TLR-4/CD14 membrane complex, NF-κB, and the inflammasome. Therefore, sCD14, overproduced by CF macrophages, originates primarily from the endocytosis/exocytosis process and should be considered to be a danger-associated molecular pattern. This elucidation of the origin and inflammation-induced mechanisms associated with sCD14 contributes to our understanding of maintained tissue inflammation.
ISSN: 0892-6638

hal-01526434
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434/file/Soluble%20CD14%20acts%20as%20a%20DAMP%20in%20human-accepted.pdf
PUBMED : 28122919

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) : HAL CCSD Springer Verlag
Résumé : International audience
Interleukin-33 (IL-33), a cytokine belonging to the IL-1 family, is crucially involved in inflammatory pathologies including liver injury and linked to various modes of cell death. However, a link between IL-33 and necroptosis or programmed necrosis in liver pathology remains elusive. We aimed to investigate the regulation of IL-33 during necroptosis-associated liver injury. The possible regulation of IL-33 during liver injury by receptor-interacting protein kinase 1 (RIPK1) and poly(ADP-ribose) polymerase 1 (PARP-1) was investigated in mice in vivo and in hepatic stellate cells in vitro. The liver immunohistopathology, flow cytometry, serum transaminase measurement, ELISA, and qPCR-based cytokine measurement were carried out. By using a chemical approach, we showed that pretreatment of mice with Necrostatin-1 (Nec-1) (inhibitor of RIPK1) and/or PJ34 (inhibitor of PARP-1) significantly protected mice against concanavalin A (ConA) liver injury (aspartate amino-transferase (AST)/alanine amino-transferase (ALT)) associated with down-regulated hepatocyte-specific IL-33 expression. In contrast, the expression level of most systemic cytokines (except for IL-6) or activation of liver immune cells was not altered by chemical inhibitors rather an increased infiltration of neutrophils in the liver. During polyinosine-polycytidylic acid (Poly(I:C))-induced acute hepatitis, liver injury and hepatocyte-specific IL-33 expression was also inhibited by PJ34 without any protective effect of PJ34 in CCl4-induced liver injury. Moreover, PJ34 down-regulated the protein expression of IL-33 in activated hepatic stellate cells by cocktail of cytokines or staurosporine in vitro. In conclusion, we evidenced that the Nec-1/PJ34 is a potent inhibitor of liver injury and Nec-1/PJ34 down-regulated hepatocyte-specific IL-33 expression in the liver in vivo or in hepatic stellate cells in vitro, suggesting IL-33 as a possible readout of necroptosis-involved liver pathologies. Necroptosis inhibitors can protect mice against liver injury induced by ConA or Poly(I:C). IL-33 expression in liver injury in vivo is inhibited by PJ34. IL-33 expression in hepatic stellate cells in vitro is inhibited by PJ34. Hepatocyte-specific IL-33 expression is down-regulated by Nec-1/PJ34 during hepatitis. IL-33 is a new marker of necroptosis-associated liver injuries.
ISSN: 0946-2716

hal-01134319
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134319
DOI : 10.1007/s00109-015-1270-6
PUBMED : 25747661