Immune sensing of food allergens promotes aversive behaviour.
Esther B Florsheim, Nathaniel D Bachtel, Jaime Cullen, Bruna G C Lima, Mahdieh Godazgar, Cuiling Zhang, Fernando Carvalho, Gregory Gautier, Pierre Launay, Andrew Wang, Marcelo O Dietrich, Ruslan Medzhitov
Author Information
Esther B Florsheim: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nathaniel D Bachtel: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Jaime Cullen: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Bruna G C Lima: Department of Pharmacology, University of São Paulo, São Paulo, SP 05508-000 SP, Brazil.
Mahdieh Godazgar: Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Cuiling Zhang: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Fernando Carvalho: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Gregory Gautier: INSERM UMRS 1149; CNRS ERL 8252; University Paris Diderot, Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX, Paris 75018, France.
Pierre Launay: INSERM UMRS 1149; CNRS ERL 8252; University Paris Diderot, Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX, Paris 75018, France.
Andrew Wang: Department of Internal Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Marcelo O Dietrich: Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Ruslan Medzhitov: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
In addition to its canonical function in protecting from pathogens, the immune system can also promote behavioural alterations . The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Using a mousefood allergy model, here we show that allergic sensitization drives antigen-specific behavioural aversion. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus, and central amygdala. Food aversion requires IgE antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote aversion requires leukotrienes and growth and differentiation factor 15 (GDF15). In addition to allergen-induced aversion, we find that lipopolysaccharide-induced inflammation also resulted in IgE-dependent aversive behaviour. These findings thus point to antigen-specific behavioural modifications that likely evolved to promote niche selection to avoid unfavourable environments.
