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.

Comparison of atopic features between children and adults with eosinophilic esophagitis

“…21 Animal models have shown a potential role for aeroallergens eliciting EoE using dust mites, cockroaches, and Aspergillus. 22,23 Rayapudi et al found in 236 children, 38% had sensitizations to indoor allergens, particularly cockroach and dust mite. 23 Gonsalves et al studied 50 adults and 30% had isolated positive SPT to aeroallergens, most commonly to pollen and dust mite.…”

“…22,23 Rayapudi et al found in 236 children, 38% had sensitizations to indoor allergens, particularly cockroach and dust mite. 23 Gonsalves et al studied 50 adults and 30% had isolated positive SPT to aeroallergens, most commonly to pollen and dust mite. 16 The pathogenesis of EoE is still not entirely clear.…”

Adult versus pediatric eosinophilic esophagitis: important differences and similarities for the clinician to understand

“…For example, adult patients seem to present a higher proportion of IgE-mediated positive allergy results than children in whom sensitization to both indoor and outdoor antigens have been documented [20,25]. Both types of antigens have been demonstrated to cause experimental EoE [26]. As noted above, seasonal variation in the diagnosis and severity of EoE has been reported for both children [27] and adults [16], and after that, some researchers have posed that airborne-antigens may trigger and help to maintain EoE, even when no clinical human trials have been conducted to undoubtedly demonstrate air-borne allergens as EoE triggers.…”

Primary eosinophilic oesophagitis in children

“…Obserwację tę potwierdziło wielu innych badaczy -diagnostyka w kierunku alergii pokarmowej należy obecnie do standardu diagnostycznego EoE, ale jak wskazuje ogól-noświatowe badanie gastrologów, obecnie 77% dzieci i tylko 16% dorosłych z EoE jest badanych w kierunku alergii pokarmowej [1,2,7,11]. Na modelach eksperymentalnych udowodniono, że alergeny kurzu domowego i pleśni mogą również powodować powstanie nacieków eozynofilowych w przełyku [12]. Jak wskazują badania z ostatnich lat, nieliczni chorzy, u których nie udaje się potwierdzić uczulenia, lokalnie -w błonie ślu-zowej przełyku -syntetyzują IgE [13].…”