Immune sensing of food allergens promotes aversive behaviour

Abstract

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 mouse food 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.

Is food preference innate instinct driven or human's free will?

“…An interesting example for food preference decisions beyond taste and hedonic value is immune sensing of food allergens (Florsheim et al, 2023). Studies have shown that humans suffering from food allergies—sometimes mismatched with “picky eaters”—learn to make food preference or aversion decisions to avoid the intake of allergens being harmful to their health (Plum et al, 2023; Rothenberg, 2023).…”

Th2 cells in rapid immune responses and protective avoidance reactions

“…Mice were immunized with ovalbumin (OVA) egg white protein in alum gel that evokes high concentrations of anti-OVA IgE antibody. 12,13 After drinking OVA water, OVA-allergic but not controlled mice developed allergic inflammation in the stomach and small intestines with diarrhea. OVA-allergic and control mice were then offered drinking water without and with OVA.…”

“…Challenge of sensitized mice once with OVA resulted in neuronal activation that was detected biochemically in brain tissue from the nucleus tractus solitarius, external lateral parabrachial nucleus, and central amygdala. 12 However, no decrease in antigen avoidance was observed after disruption of input from the vagus nerve or dorsal root sensory neurons that transmit signals from internal organs, including the gastrointestinal tract, through the nucleus tractus solitarius to the parabrachial nucleus (PBN). Levels of growth and differentiation factor 15 (GDF15) were increased significantly in gastrointestinal epithelial cells of antigen-avoiding mice through a mast cell-and IgE-dependent pathway.…”

“…The specificity of leukotriene mediation was suggested by the normal avoidance behavior of mice genetically deficient in other mast cell mediators, including histamine, serotonin, and several proteases. 12,13 A central role for the cysteinyl-leukotrienes was implied initially by finding a 7-to 25-fold increase in the duodenal tissue level of LTE4 in orally challenged OVAallergic mice relative to that of control unchallenged and LTC4 synthase-knockout OVA-allergic mice. That cysteinyl (Cys)-leukotrienes are the major mediator of antigen avoidance was further documented by lack of avoidance in LTC4 synthase-knockout mice and mice treated with CysLTR2 inhibitor HAM13379.…”

“…A new possibility has been identified from the results of studies of food allergy in rodents (Figure 2). Mice were immunized with ovalbumin (OVA) egg white protein in alum gel that evokes high concentrations of anti‐OVA IgE antibody 12,13 . After drinking OVA water, OVA‐allergic but not controlled mice developed allergic inflammation in the stomach and small intestines with diarrhea.…”