Immune sensing of food allergens promotes avoidance behaviour

• Published in: Nature (London) Vol. 620; no. 7974; pp. 643 - 650
• Main Authors: Florsheim, Esther B, Bachtel, Nathaniel D, Cullen, Jaime L, Lima, Bruna G C, Godazgar, Mahdieh, Carvalho, Fernando, Chatain, Carolina P, Zimmer, Marcelo R, Zhang, Cuiling, Gautier, Gregory, Launay, Pierre, Wang, Andrew, Dietrich, Marcelo O, Medzhitov, Ruslan
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 17.08.2023; Nature Publishing Group UK
• Subjects: Allergens; Allergens - immunology; Allergies; Amygdala; Animal models; Animals; Antibodies; Antigens; Avoidance; Avoidance behavior; Avoidance Learning - physiology; Brain; Central Amygdaloid Nucleus - physiology; Disease Models, Animal; Food; Food allergies; Food Hypersensitivity - genetics; Food Hypersensitivity - immunology; Hypothalamus; Immune system; Immunoglobulin E; Immunoglobulin E - immunology; Inflammation; Ingestion; Intestines - immunology; Leukotrienes; Mast cells; Mast Cells - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nervous system; Parabrachial nucleus; Parabrachial Nucleus - physiology; Solitary Nucleus - physiology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-023-06362-4

In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour . The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus and central amygdala. Allergen avoidance requires immunoglobulin E (IgE) antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote avoidance requires cysteinyl leukotrienes and growth and differentiation factor 15. Finally, a comparison of C57BL/6 and BALB/c mouse strains revealed a strong effect of the genetic background on the avoidance behaviour. These findings thus point to antigen-specific behavioural modifications that probably evolved to promote niche selection to avoid unfavourable environments.