Commensal bacteria signal through TLR5 and AhR to improve barrier integrity and prevent allergic responses to food
Andrea M. Kemter,
Robert T. Patry,
Jack Arnold,
Lauren A. Hesser,
Evelyn Campbell,
Edward Ionescu,
Mark Mimee,
Shan Wang,
Cathryn R. Nagler
Affiliations
Andrea M. Kemter
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA
Robert T. Patry
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA
Jack Arnold
Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA
Lauren A. Hesser
Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA
Evelyn Campbell
Committee on Microbiology, The University of Chicago, Chicago, IL 60637, USA
Edward Ionescu
Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA
Mark Mimee
Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA; Committee on Microbiology, The University of Chicago, Chicago, IL 60637, USA
Shan Wang
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA
Cathryn R. Nagler
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA; Committee on Immunology, The University of Chicago, Chicago, IL 60637, USA; Corresponding author
Summary: 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.
