biostudies-literatureKemter AMNIDDK NIH HHSNIAID NIH HHSNIGMS NIH HHS113153https://www.ebi.ac.uk/biostudies/studies/S-EPMC10697505biostudies-literatureUnknown42(10)The increasing prevalence of food allergies has been linked to reduced commensal microbial diversity. In this article, we describe two features of allergy-protective Clostridia that contribute to their beneficial effects. Some Clostridial taxa bear flagella (a ligand for TLR5) and produce indole (a ligand for the aryl hydrocarbon receptor [AhR]). Lysates and flagella from a Clostridia consortium induced interleukin-22 (IL-22) secretion from ileal explants. IL-22 production is abrogated in explants from mice in which TLR5 or MyD88 signaling is deficient either globally or conditionally in CD11c⁺ antigen-presenting cells. AhR signaling in RORγt⁺ cells is necessary for the induction of IL-22. Mice deficient in AhR in RORγt⁺ cells exhibit increased intestinal permeability and are more susceptible to an anaphylactic response to food. Our findings implicate TLR5 and AhR signaling in a molecular mechanism by which commensal Clostridia protect against allergic responses to food.Cell reportsCommensal bacteria signal through TLR5 and AhR to improve barrier integrity and prevent allergic responses to food.PMC10697505R01 AI106302R25 GM109439R01 AI146099P30 DK042086Patry RTArnold JMimee MCampbell EWang SNagler CRHesser LAIonescu EKemter AMfalseCommensal bacteria signal through TLR5 and AhR to improve barrier integrity and prevent allergic responses to food.The increasing prevalence of food allergies has been linked to reduced commensal microbial diversity. In this article, we describe two features of allergy-protective Clostridia that contribute to their beneficial effects. Some Clostridial taxa bear flagella (a ligand for TLR5) and produce indole (a ligand for the aryl hydrocarbon receptor [AhR]). Lysates and flagella from a Clostridia consortium induced interleukin-22 (IL-22) secretion from ileal explants. IL-22 production is abrogated in explants from mice in which TLR5 or MyD88 signaling is deficient either globally or conditionally in CD11c⁺ antigen-presenting cells. AhR signaling in RORγt⁺ cells is necessary for the induction of IL-22. Mice deficient in AhR in RORγt⁺ cells exhibit increased intestinal permeability and are more susceptible to an anaphylactic response to food. Our findings implicate TLR5 and AhR signaling in a molecular mechanism by which commensal Clostridia protect against allergic responses to food.2023-01-01T00:00:00Z2023 Oct2026-05-28T23:55:29.725Z2024-10-18T06:31:53.642ZS-EPMC106975053774218510.1016/j.celrep.2023.113153