Immune sensing of food allergens promotes avoidance behaviour

Esther B. Florsheim (), Nathaniel D. Bachtel, Jaime L. Cullen, Bruna G. C. Lima, Mahdieh Godazgar, Fernando Carvalho, Carolina P. Chatain, Marcelo R. Zimmer, Cuiling Zhang, Gregory Gautier, Pierre Launay, Andrew Wang, Marcelo O. Dietrich and Ruslan Medzhitov ()
Additional contact information
Esther B. Florsheim: Yale University School of Medicine
Nathaniel D. Bachtel: Yale University School of Medicine
Jaime L. Cullen: Yale University School of Medicine
Bruna G. C. Lima: Arizona State University
Mahdieh Godazgar: Yale University School of Medicine
Fernando Carvalho: Yale University School of Medicine
Carolina P. Chatain: Yale University School of Medicine
Marcelo R. Zimmer: Yale University School of Medicine
Cuiling Zhang: Yale University School of Medicine
Gregory Gautier: Centre de Recherche sur l’Inflammation, INSERM UMR1149, CNRS EMR8252, Université Paris Cité
Pierre Launay: Centre de Recherche sur l’Inflammation, INSERM UMR1149, CNRS EMR8252, Université Paris Cité
Andrew Wang: Yale University School of Medicine
Marcelo O. Dietrich: Yale University School of Medicine
Ruslan Medzhitov: Yale University School of Medicine

Nature, 2023, vol. 620, issue 7974, 643-650

Abstract: Abstract In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour1,2. 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.

Date: 2023
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DOI: 10.1038/s41586-023-06362-4

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