Innate and Adaptive Immunity Interact to Quench Microbiome Flagellar Motility in the Gut

Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find tha...

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Bibliographic Details
Published in:Cell host & microbe 2013-11, Vol.14 (5), p.571-581
Main Authors: Cullender, Tyler C., Chassaing, Benoit, Janzon, Anders, Kumar, Krithika, Muller, Catherine E., Werner, Jeffrey J., Angenent, Largus T., Bell, M. Elizabeth, Hay, Anthony G., Peterson, Daniel A., Walter, Jens, Vijay-Kumar, Matam, Gewirtz, Andrew T., Ley, Ruth E.
Format: Article
Language:English
Subjects:
Adaptive Immunity
Animals
Flagella - immunology
Flagellin - immunology
Gastrointestinal Tract - immunology
Gastrointestinal Tract - microbiology
Immunity, Innate
Immunity, Mucosal
Immunoglobulin A - immunology
Locomotion
Mice
Mice, Knockout
Microbiota - immunology
Toll-Like Receptor 5 - deficiency
Toll-Like Receptor 5 - immunology
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Summary:Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5−/− gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5−/− host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome’s production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis. •TLR5−/− mice have reduced levels of anti-flagellin antibodies in the gut•Flagella-related genes of commensal microbes are upregulated in TLR5−/− mouse guts•Antibodies against flagellin induce downregulation of flagella genes•Flagellated bacteria penetrate TLR5−/− small intestinal villi and mucosal barrier
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2013.10.009