Commensal bacteria signal through TLR5 and AhR to improve barrier integrity and prevent allergic responses to food

Cell Rep. 2023 Oct 31;42(10):113153. doi: 10.1016/j.celrep.2023.113153. Epub 2023 Sep 25.

Abstract

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.

Keywords: AhR; CP: Immunology; IL-22; Microbiology; TLR5; barrier immunity; food allergy; microbiome; oral tolerance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens
  • Animals
  • Bacteria
  • Hypersensitivity*
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Aryl Hydrocarbon
  • Toll-Like Receptor 5*

Substances

  • Allergens
  • Ligands
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Aryl Hydrocarbon
  • Toll-Like Receptor 5
  • Tlr5 protein, mouse
  • Ahr protein, mouse