Propriétés des anticorps des muqueuses

Les anticorps des muqueuses comprennent différentes immunoglobulines, principalement des IgA sécrétoires et des IgG locales, qui forment la première ligne de défense immunitaire contre les agents pathogènes. Ils constituent la majeure partie des immunoglobulines synthétisées par l’organisme et proviennent principalement du système immunitaire sécrétoire, qui est indépendant du reste du système immunitaire. Ces anticorps agissent par deux mécanismes originaux : l’exclusion et l'élimination immunes. Ils comprennent des anticorps classiques, induits par l’antigène, ainsi que des anticorps naturels polyréactifs préimmuns. Les progrès récents dans ce domaine suggèrent de nouvelles approches du problème des vaccinations muqueuses

Regioselective conversion of lactams to thiolactams

International audienc

Impairment by Mucosal Adjuvants and Cross-Reactivity with Variant Peptides of the Mucosal Immunity Induced by Injection of the Fusion Peptide PADRE-ELDKWA

Secretory immunity protects against mucosal transmission of viruses, as demonstrated with the oral poliovirus vaccine. In a previous study we showed that this immunity could be induced in mice by injection of a fusion peptide consisting of an unnatural peptide-like sequence (PADRE) and a viral epitope (ELDKWASLW). PADRE is a T-helper-cell epitope able to bind most major histocompatibility complex class II molecules of different haplotypes in mice and humans and to increase antibody responses. ELDKWA is a well-known consensual sequence of gp41 involved in a key structure of human immunodeficiency virus (HIV) type 1. Here, the antibody response to the native form of ELDKWA was mainly of the immunoglobulin A isotype and selectively occurred in mucosa. Adjuvants, such as cholera toxin and cytosine polyguanine, were useless and even competed with PADRE for the response. Interestingly, these antibodies were cross-reactive with the three major variants of the epitope, as shown both by direct enzyme-linked immunosorbent assay and by inhibition. This unconventional route of mucosal immunization allows control of the administered dose. The lack of adjuvant and the cross-reactivity of the antibodies increase the safety and the spectrum of the candidate vaccine, respectively. The drug-like nature of the construct suggests further improvements by synthesis of more antigenic sequences. The reasonable cost of short peptides at the industrial level and their purity make this approach of interest for future vaccines against mucosal transmission of HIV or other pathogens

Les moulins à eau du Pays de Louviers

[Sous la direction de Bodinier Bernard

A direct aspiration, first pass technique (adapt) versus stent retrievers for acute stroke therapy: an observational comparative study

International audienceOBJECTIVE: Mechanical thrombectomy with stent retrievers is now the standard therapy for selected patients with ischemic stroke. The technique of A Direct Aspiration, First Pass Technique for the Endovascular Treatment of Stroke (ADAPT) appears promising with a high rate of recanalization. We compared ADAPT versus stent retrievers (the Solitaire device) for efficacy and safety as a front-line endovascular procedure.METHODS: We analyzed 243 consecutive patients with large intracranial artery occlusions of the anterior circulation, treated within 6 hours with mechanical thrombectomy by either ADAPT or the Solitaire stent. Th primary outcome was complete recanalization (modified TICI ≥ 2b); secondary outcomes included complication rates and procedural and clinical outcomes.RESULTS: From November 2012 to June 2014, 119 patients were treated with stent retriever (Solitaire FR) and 124 by using the ADAPT with Penumbra reperfusion catheters. The median baseline NIHSS score was the same for both groups (Solitaire, 17 [interquartile range, 11-21] versus ADAPT, 17 [interquartile range, 12-21]). Time from groin puncture to recanalization (Solitaire, 50 minutes [range, 25-80 minutes] versus ADAPT, 45 minutes [range, 27-70 minutes], PPPCONCLUSIONS: Front-line ADAPT achieved higher recanalization rates than the Solitaire device. Further randomized controlled trials are warranted to define the best strategy for mechanical thrombectomy

Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNF overproduction in response to microbial products.

International audienceHIV infects activated CD4⁺ T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNFα. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNFα production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3)⁺ and CD1c (BDCA-1)⁺ dendritic cell counts were reduced. Conversely, CD14⁺ CD16⁺⁺ monocyte counts were increased, particularly those expressing M-DC8, while classical CD14⁺⁺ CD16⁻ M-DC8⁻ monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNFα in response to LPS than those from virologically suppressed patients. M-DC8⁺ monocytes were mostly responsible for this overproduction. Moreover, M-DC8⁺ monocytes differentiated in vitro from classical monocytes using M-CSF and GM-CSF, which is increased in viremic patient's plasma. This M-DC8⁺ monocyte population, which is involved in the pathogenesis of chronic inflammatory diseases like Crohn disease, might thus be considered as a major actor in the immune hyperactivation fueling HIV infection progression

Quasi-static Load Sharing Model in the Case of Moulded Glass Fibre Reinforced Polyamide 6 Gears

International audienceThis paper presents a fast and efficient computational method to predict the mechanicalbehaviour of plastic cylindrical gears made of fibre reinforced polyamide 6. Based on this method, aninvestigation on the relation between the fibre orientation and the gear behaviour is done. Thenumerical method uses a viscoelastic model accounting for the temperature, humidity and rotationalspeed dependence of the gear. This model is developed under the assumption that the material isstressed in its linear domain. The method is performed in three steps: the first one consists of definingthe fibre orientation from simulation and experimental results. The second step characterises theviscoelastic behaviour of the material. The third step consists in calculating the load sharing with localmeshing, which integrates the viscoelastic model over the entire surface of the tooth. This modelpermits computation of the load sharing between instantaneously engaged teeth and provides resultssuch as contact pressure, tooth root stress and transmission error. Three fibre orientation models withan increasing complexity are compared. Simulation results show a limited influence of the fibreorientation on the contact pressure and tooth root stress, nevertheless difference up to 10% areobserved on the transmission error amplitude