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Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma
Dijoux Eléonore,Klein Martin,Misme-Aucouturier Barbara,Cheminant Marie-Aude,de Carvalho Marion,Collin Louise,Hassoun Dorian,Delage Erwan,Gourdel Mathilde,Loirand Gervaise,Sauzeau Vincent,Magnan Antoin 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.2
Purpose: Asthma is a frequent chronic inflammatory bronchial disease affecting more than 300 million patients worldwide, 70% of whom are secondary to allergy. The diversity of asthmatic endotypes contributes to their complexity. The inter-relationship between allergen and other exposure and the airway microbiome adds to the phenotypic diversity and defines the natural course of asthma. Here, we compared the mouse models of house dust mite (HDM)-induced allergic asthma. Allergic sensitization was performed via various routes and associated with outcomes. Methods: Mice were sensitized with HDM via the oral, nasal or percutaneous routes. Lung function, barrier integrity, immune response and microbiota composition were analyzed. Results: Severe impairment of respiratory function was observed in the mice sensitized by the nasal and cutaneous paths. It was associated with epithelial dysfunction characterized by an increased permeability secondary to junction protein disruption. Such sensitization paths induced a mixed eosinophilic and neutrophilic inflammatory response with high interleukin (IL)-17 airway secretion. In contrast, orally sensitized mice showed a mild impairment of respiratory function. Epithelial dysfunction was mild with increased mucus production, but preserved epithelial junctions. Regarding lung microbiota, sensitization provoked a significant loss of diversity. At the genus level, Cutibacterium, Acinetobacter, Streptococcus and Lactobacillus were found to be modulated according to the sensitization pathway. An increase in theanti-inflammatory microbiota metabolites was observed in the oral-sensitization group. Conclusions: Our study highlights the strong impact of the sensitization route on the pathophysiology and the critical phenotypic diversity of allergic asthma in a mouse model.
( Renata Vinholes Oliveira Da Rocha ),( Maria Isabel Morgan Martins ),( Flavia Tasmim Techera Antunes ),( Marcia Gerhardt Martins ),( Adriane Belló Klein ),( Dione Silva Corrêa ),( Alessandra Hubner D 대한폐경학회 2021 대한폐경학회지 Vol.27 No.3
Objectives: Menopause induces changes in neuronal transmission, leading to anxiety and depression. Changes in the brain’s glutamate levels cause psychological behavior in postmenopausal women. Omega-3 has been studied to improve some of these behaviors. Methods: Twenty-four female Wistar rats were divided into four groups: sham-operated treated with water (SO-W), sham-operated treated with omega-3 (SO-O), ovariectomized (OVX) treated with water (OVX-W), and bilateral OVX treated with omega-3 (OVX-O). These treatments were performed for 20 days via gavage, before and after surgery, totaling 40 days. Results: In the forced swimming, elevated plus-maze, and open field tests to assess behaviors, such as depression and anxiety, omega-3 improved these behaviors in both treated groups. The levels of thiobarbituric acid reactive substances (TBARS) in the brain were not different between the groups; however, there was a significant decrease in the catalase activity in the SO-O group compared with the SO-W group (P < 0.05). The glutamate level in the cerebrospinal fluid (CSF) was elevated in the SO-O group (P < 0.001) but not in the OVX-W or OVX-O groups. Conclusions: These results bring novel data when related to the glutamatergic system in the SO-O group. This has suggested that the action mechanism of omega-3 was not dependent on glutamate levels in the CSF of the OVX group, but it played a regulatory role in the sham-operated animals. To confirm this, more studies are needed to explore this field when relating to the estrogen and glutamate receptor changes in specific brain regions.