Allergic inflammation drives avoidance and anxiety behaviors 2974

Abstract Description Beyond immunity, inflammation impacts brain function and behavior. Inflammatory signals provide input to the nervous system, helping identify harmful stimuli and generate adaptive responses. While sickness behaviors induced by pathogens are well-characterized, how immune sensing affects behavior in allergies remains unknown. We hypothesized that allergic inflammation, compared with infection, drives behaviors. Using integrated approaches from immunology, neuroscience, and behavior, we investigated how food allergies influence brain activation and behavior in mice. Our findings reveal that allergic sensitization induces allergen-specific, long-lasting avoidance behaviors that precede allergic symptoms such as gut inflammation, altered motility, and anaphylaxis. Allergen exposure activated brain regions (e.g., NTS, PBN, CeA) in allergic but not control mice. Mechanistically, allergen-induced avoidance requires leukotrienes, IgE, and mast cell FcεRI expression. We propose that the immune system recognizes allergens in the gastrointestinal mucosa, activating central pathways via soluble mediators to drive food aversion and limit exposure. Importantly, chronic allergen exposure intensifies immune and behavioral responses, resulting in anxiety-like behaviors, highlighting a transition from protective to detrimental outcomes. These findings underscore the functional coupling of immune and nervous systems in food sensing, shedding light on allergy-related mental health risks. Funding Sources Hypothesis Fund ($150k) PI: Esther Borges Florsheim 01/01/2024-05/31/2025 Food Allergy Science Initiative ($75k) PI: Esther Borges Florsheim 01/09/21-31/08/25 *None of the funding sources cover meetings and traveling expenses. Topic Categories Neuroimmunology (NEUR)