Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development
| العنوان: | Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development |
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| المؤلفون: | Thomas B. Nutman, Sandra Bonne-Année, Joshua Sciurba, Erik P. Karmele, Pedro Henrique Gazzinelli-Guimarães, Alessandra Ricciardi, Ricardo Toshio Fujiwara, Rafael de Queiroz Prado |
| المصدر: | Journal of Clinical Investigation. 129:3686-3701 |
| بيانات النشر: | American Society for Clinical Investigation, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Swine, Biology, Allergic inflammation, Type 2 immune response, Allergic sensitization, Mice, 03 medical and health sciences, Th2 Cells, 0302 clinical medicine, Hypersensitivity, medicine, Animals, Antigens, Dermatophagoides, Lung, Sensitization, Inflammation, Antigen Presentation, Ascariasis, Mice, Inbred BALB C, Innate immune system, Ascaris, Macrophages, Pyroglyphidae, Innate lymphoid cell, General Medicine, Allergens, Eosinophil, biology.organism_classification, Asthma, Immunity, Innate, Eosinophils, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, Female, Research Article |
| الوصف: | This study investigates the relationship between helminth infection and allergic sensitization by assessing the influence of preexisting allergy on the outcome of helminth infections, rather than the more traditional approach in which the helminth infection precedes the onset of allergy. Here we used a murine model of house dust mite–induced (HDM-induced) allergic inflammation followed by Ascaris infection to demonstrate that allergic sensitization drives an eosinophil-rich pulmonary type 2 immune response (Th2 cells, M2 macrophages, type 2 innate lymphoid cells, IL-33, IL-4, IL-13, and mucus) that directly hinders larval development and reduces markedly the parasite burden in the lungs. This effect is dependent on the presence of eosinophils, as eosinophil-deficient mice were unable to limit parasite development or numbers. In vivo administration of neutralizing antibodies against CD4 prior to HDM sensitization significantly reduced eosinophils in the lungs, resulting in the reversal of the HDM-induced Ascaris larval killing. Our data suggest that HDM allergic sensitization drives a response that mimics a primary Ascaris infection, such that CD4(+) Th2-mediated eosinophil-dependent helminth larval killing in the lung tissue occurs. This study provides insight into the mechanisms underlying tissue-specific responses that drive a protective response against the early stages of the helminths prior to their establishing long-lasting infections in the host. |
| تدمد: | 1558-8238 0021-9738 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55e7ba21c5b94143d20af0bda6a7dbe6 https://doi.org/10.1172/jci127963 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....55e7ba21c5b94143d20af0bda6a7dbe6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15588238 00219738 |
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