Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice

Abstract

EE is an emerging disease reported in children and adults of urbanized countries, where indoor insect allergens are major health risk factors. Review of our hospital patient database uncovered that a number of EE patients have hypersensitivity to indoor cat, dog, cockroach, and dust mite allergens. We tested the hypothesis whether inhaled indoor insect allergens are effective inducers of experimental EE. We delivered cat, dog, cockroach, and dust mite allergen extracts intranasally to wild-type and eotaxin-1/2-, CCR3-, and IL-5-deficient mice. Interestingly, wild-type mice exposed to cockroach or dust mite allergens develop a significant increase in the levels of esophageal eosinophils and mast cells compared with saline-challenged mice. The eosinophil numbers in the esophagus of cockroach- and dust mite-exposed mice were 18.3+/-6.8/mm2 and 33.4+/-11.1/mm2 compared with 2.3+/-1.8/mm2 and 2.1+/-1.2/mm2 in saline-challenged mice. Additionally, we observed an additive effect of these two allergens in inducing esophageal eosinophilia and mastocytosis. Histopathological analysis detected intraepithelial esophageal eosinophilia in mice exposed to both allergens. Furthermore, mice exposed to cockroach and/or dust mite had increased levels of total IgE and antigen-specific IgG1 in the blood and increased esophageal expression of eosinophil-active cytokines (IL-13) and chemokines (eotaxin-1). Notably, mice deficient in eotaxin-1/2, CCR3, and IL-5 showed ablated esophageal eosinophilia following cockroach or dust mite allergen exposure. These data indicate that indoor insect allergens are potent inducers of IL-5 and eotaxin-mediated esophageal eosinophilia. These experimental studies are in accordance with clinical data but may have some limitations inherent to animal models of human disease.