Efficacy of epicutaneous immunotherapy (EPIT) in a new model of peanut-induced eosinophilic esophagitis (EoE) and allergic enterpathy (AE)

Background Eosinophilia is often linked to allergic gastrointestinal disorders linked to food allergy. EPIT using Viaskin® device has been described as a therapeutic method in food allergy. We developed a model of mice sensitized to peanut, exhibiting EoE and AE after exclusive feeding with peanut protein extracts (PPE). This study was conducted in order to evaluate the efficacy of EPIT. Methods After oral sensitization with PPE and cholera toxin, 30 BALB/c mice were treated weekly during 8 weeks by PPE skin applications (EPIT), 20 mice were not treated (Sham) and 10 mice constituted the control group (C). Mice were then exclusively fed with PPE. Specific IgE, IgG1 and IgG2a were monitored during immunotherapy. Esophageal and jejunal samples were taken for histological analyses. Results sIgE increased after oral sensitization, respectively 0.207 ±0.03 and 0.214±0.04 μg/ml, in EPIT and Sham, with undetectable values in C. Following EPIT, sIgE decreased and sIgG2a increased, respectively 0.139±0.01 vs 0.166±0.01 μg/ml (EPIT vs Sham, p<0.05) and 14.96 ±0.60 vs 4.73±1.75 μg/ml (p<0.05). Esophageal eosinophilic infiltration (measured in 6 high power fields) was higher in Sham, 136±32, than in EPIT, 50±12 (p<0.05) and C, 7±3 cells/mm2 (p<0.01). Esophagus mucosa thickness was increased in Sham compared to EPIT and C (p<0.001). Sham group exhibited higher mRNA levels of cytokines than EPIT: eotaxin (p<0.05), IL-5 (p<0.05), IL-13 (p<0.05). The mRNA levels of these cytokines in EPIT were similar to C. The expression of Foxp3 mRNA increased significantky after EPIT compared with Sham and C (p<0.05). The jejunal villus/crypt ratio was lower in Sham than in EPIT and C, respectively 1.6 ±0.1 vs 2.3±0.2 (p<0.01) and 2.4±0.1 (p<0.001). Eosinophilic infiltration in jejunum was increased in Sham compared to EPIT (p<0.01) and C (p<0.001). Conclusion EPIT is effective in preventing EoE and AE induced by oral challenge in mice sensitized to peanut

Epicutaneous Immunotherapy (EPIT) Blocks the Allergic Esophago-Gastro-Enteropathy Induced by Sustained Oral Exposure to Peanuts in Sensitized Mice

Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes. Methods: Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. Results: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm2) and reduced villus/crypt ratios (1.660.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm2, p,0.05), mRNA expression of Th2 cytokines in tissue - eotaxin (p,0.05), IL-5 (p,0.05), and IL-13 (p,0.05) -, GATA-3 (p,0.05), and intestinal villus sub-atrophia (2.360.15). EPIT also increased specific IgG2a (p,0.05) and mRNA expression of Foxp3 (p,0.05) in the esophageal mucosa. Conclusions: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT

Towards the Establishment of a Porcine Model to Study Human Amebiasis

BACKGROUND: Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i) the trophozoite, growing in the intestine and (ii) the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. METHODOLOGY/PRINCIPAL FINDINGS: We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. CONCLUSIONS: The pig model could help with simultaneously studying intestinal and extraintestinal lesion development

How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property

The modern concept of ‘dynasty’ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegel’s references to ‘dynasty’, read with Marx’s critique, further show how ‘dynasty’ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about ‘dynasty’ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of ‘dynasty’ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/‘tribal’ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ‘rajavamshi’ and ‘Kshatriya’. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe

Histoire des amours de Chereas et de Callirrhoë : par Pierre-Henri Larcher; trad. du Grec, avec des remarques.

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Treatment of eosinophilic gastritis by epicutaneous immunotherapy (EPIT) in peanut allergic piglets

Treatment of eosinophilic gastritis by epicutaneous immunotherapy (EPIT) in peanut allergic piglets. Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunolog

Treatment of colitis by epicutaneous immunotherapy in a murine model

Treatment of colitis by epicutaneous immunotherapy in a murine mode

Preclinical Evaluation of a Novel Epicutaneous Vaccine against Respiratory Syncytial Virus

International audienceIn order to be able to put an RSV vaccine onto the market, new vaccination strategies combining scientific and technical innovation need to be explored. In the present project, we describe the development and the non-clinical evaluation of an original epicutaneous RSV vaccine that combines two patented technologies: Viaskin® epicutaneous patches developed by DBV Technologies as a delivery platform, and RSV N-nanorings fused to the F epitope targeted by palivizumab (N-FsII) developed by the French National Institute for Agronomical Research (INRA) as a subunit antigen. We have demonstrated that Viaskin® loaded with a formulation containing N-FsII antigen (Viaskin®- N-FsII) is highly immunogenic in mice and promote a Th1/Th17 oriented immune response. More importantly, Viaskin®-N-FsII epicutaneous vaccine confers a high level of protection against viral replication upon RSV challenge in mice, without exacerbating clinical symptoms. In swine, which provides the best experimental model for the cutaneous passage of drug/antigen in human skin, we have demonstrated that Viaskin®-N-FsII induced a significant RSV N-specific T-cell response. Using this animal model, we have also shown that GFP fluorescent N-nanorings, delivered epicutaneously with Viaskin® patches, are taken up by epidermal Langerhans cells. In conclusion, Viaskin®-N-FsII epicutaneous vaccine seems efficient to protect against RSV infection in animal model. Moreover, since no injection is required and no skin conditioning is needed before application of patches, Viaskin®-N-FsII epicutaneous vaccine would provide a pertinent and safe solution for the vaccination of newborns