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PMID: 24237702 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut.

Cell host & microbe ·Vol. 14 ·No. 5 ·2013-11-13 ·Pages 571-81

Cullender TC, Chassaing B, Janzon A, Kumar K, Muller CE, Werner JJ, Angenent LT, Bell ME, Hay AG, Peterson DA, Walter J, Vijay-Kumar M, Gewirtz AT, Ley RE

Abstract

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.

MeSH Terms
Adaptive Immunity Animals Flagella/immunology Flagellin/immunology Gastrointestinal Tract/immunology,microbiology Immunity, Innate Immunity, Mucosal Immunoglobulin A/immunology Locomotion Mice Mice, Knockout Microbiota/immunology Toll-Like Receptor 5/deficiency,immunology
Chemicals
Immunoglobulin A Toll-Like Receptor 5 Flagellin
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Cullender Tyler C
Department of Microbiology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
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
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Article Info
Journal
Cell host & microbe
Abbr.
Cell Host Microbe
ISSN
1934-6069
DOI
10.1016/j.chom.2013.10.009
Published
2013-11-13
Pages
571-81
Language
English
Region
United States
NLM ID
101302316
PMCID
PMC3920589
Subset
IM
Grants
NIDDK NIH HHS · R01 DK097865 · United States
NIDDK NIH HHS · R01 DK093595 · United States
NIDDK NIH HHS · R01DK093595 · United States
NIH HHS · DP2 OD007444 · United States
NIH HHS · DP2OD007444 · United States
Corrections
CommentIn
PMID: 24237694
CommentIn
PMID: 24336178
External Links
PubMed source DOI: 10.1016/j.chom.2013.10.009 PMC Full Text View journal details
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