Mouse Models for Food Allergies: Where Do We Stand?

Abstract

Food allergies are a steadily increasing health and economic problem. Immunologically, food allergic reactions are caused by pathological, allergen-specific Th2 responses resulting in IgE-mediated mast cell degranulation and associated inflammatory reactions. Clinically, food allergies are characterized by local inflammation of the mouth mucosa, the face, the throat, the gastrointestinal tract, are frequently paralleled by skin reactions, and can result in life-threatening anaphylactic reactions. To better understand food allergies and establish novel treatment options, mouse models are indispensable. This review discusses the available mouse food allergy models, dividing them into four categories: (1) adjuvant-free mouse models, (2) mouse models relying on adjuvants to establish allergen-specific Th2 responses, (3) mouse models using genetically-modified mouse strains to allow for easier sensitization, and (4) humanized mouse models in which different immunodeficient mouse strains are reconstituted with human immune or stem cells to investigate humanized immune responses. While most of the available mouse models can reproducibly portray the immunological parameters of food allergy (Th2 immune responses, IgE production and mast cell activation/expansion), so far, the recreation of the clinical parameters has proven more difficult. Therefore, up to now none of the available mouse models can reproduce the complete human pathology.

Assessment of allergenicity of irradiated dairy products in a Balb/c mice model

“…No symptoms of systemic anaphylaxis after challenge by the used model of food allergy were observed. In contrast to our results, symptoms of systemic anaphylaxis in models of C3H/HeJ and Balb/c mice in groups with increased levels of investigated antibodies were reported (Li et al 1999;Liu et al 2016;Schülke and Albrecht 2019).…”

“…So far many food allergens have been identified, but these in milk, eggs, nuts, in particular peanuts, fish, soya, wheat and crustacean are responsible for 90% of the severe reactions (Schülke and Albrecht 2019). Mostly, they are water soluble glycoproteins (usually with molecular weight 10-60 кDa), which are resistant to heat, acids and enzymes, and have a variety of epitopes (sequential and conformational), recognized by specific IgE.…”

“…Subsequent clustering of eosinophils and basophils in tissues triggers late phase reaction. The released mediators lead to clinical manifestations of allergy (itching, hives, edema, gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain, rhinitis, bronchospasm, laryngospasm, anaphylactic shock) (Liu et al 2016;Sicherer and Sampson 2018;Schülke and Albrecht 2019).…”

The use of aluminium hydroxide as adjuvant modulates the specific antibody response—A Brown Norway rat study with native and denatured cow's milk allergens

“…Further, Al(OH) 3 is the most applied adjuvant in i.p. sensitization studies in animal models of food allergy 27,28 . In both situations, Al(OH) 3 is used to increase the immune response towards the co‐formulated antigen.…”

“…Al(OH) 3 is associated with the induction of a Th2 response, thought to be a result of direct stimulation of antigen presenting cells, complement cascades and chemokines, leading to higher and more persistent production of specific antibodies against the co‐formulated allergen 24,25 . Further, the use of Al(OH) 3 is a mainstay approach in animal sensitization models 27,28 …”