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PreprintCited by 117Immune Response and InflammationGut microbiota and healthT-cell and B-cell Immunology

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Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5

Open access
Clasen, Sara J., Bell, Michael E. W., Lee, Du-Hwa, Henseler, Zachariah M., Borbón, Andrea, de la Cuesta-Zuluaga, Jacobo, Parys, Katarzyna, Zou, Jun, Youngblut, Nicholas D., Gewirtz, Andrew T., Belkhadir, Youssef, Ley, Ruth E.·2022·Science Immunology
DOI 10.1101/2022.04.12.488020

Preprint — published as 10.1126/sciimmunol.abq7001

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Abstract

Flagellin, the protein unit of the bacterial flagellum, stimulates the innate immune receptor Toll-like receptor (TLR)5 following pattern recognition, or evades TLR5 through lack of recognition. This binary response fails to explain the weak agonism of flagellins from commensal bacteria, raising the question of how TLR5 response is tuned. Here, we describe a novel class of flagellin-TLR5 interaction, termed silent recognition. Silent flagellins are weak agonists despite high affinity binding to TLR5. This dynamic response is tuned by TLR5-flagellin interaction distal to the site of pattern recognition. Silent flagellins are produced primarily by the abundant gut bacteria Lachnospiraceae and are enriched in non-Western populations. These findings provide a mechanism for the innate immune system to tolerate commensal-derived flagellins. One-Sentence Summary: TLR5 sensitively recognizes, but responds weakly to, flagellins from gut commensal bacteria.

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Metadata

Authors
Clasen, S. J., Bell, M. E. W., Lee, D.-H., Henseler, Z. M., Borbón, A., de la Cuesta-Zuluaga, J., Parys, K., Zou, J., Youngblut, N. D., Gewirtz, A. T., Belkhadir, Y., & Ley, R. E.
Affiliations
  • Max Planck Institute for Biology (DE)
  • Gregor Mendel Institute of Molecular Plant Biology (AT)
  • Georgia State University (US)
Corresponding author
Ley, Ruth E.
ORCID
Venue
Science Immunology
Publisher
openRxiv
Published
2022-04-12
Volume
8
Issue
79
Pages
eabq7001-eabq7001
ISSN
2470-9468 (ISSN-L)
DOI
10.1101/2022.04.12.488020
OpenAlex
W4313706743
Cited by
117
References
1
Citations by year
2026: 25 · 2025: 37 · 2024: 37 · 2023: 16 · 2022: 1
FWCI
12.70
Type
journal article
Language
en
Open access
Locations
  • Science Immunology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
Funders
  • Vienna Science and Technology Fund (LS17-047)
  • Max-Planck-Gesellschaft
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
flagellin, TLR5, gut commensal bacteria, innate immune tolerance, Lachnospiraceae, human gut microbiome, Salmonella flagellin, human organoids
MeSH terms
Animals, Bacteria, Flagellin, Humans, Intestines, Signal Transduction, Toll-Like Receptor 5, Mice

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