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

View ORCID ProfileSara J. Clasen, Michael E. W. Bell, View ORCID ProfileDu-Hwa Lee, Zachariah M. Henseler, View ORCID ProfileAndrea Borbón, View ORCID ProfileJacobo de la Cuesta-Zuluaga, View ORCID ProfileKatarzyna Parys, View ORCID ProfileJun Zou, Nicholas D. Youngblut, View ORCID ProfileAndrew T. Gewirtz, View ORCID ProfileYoussef Belkhadir, View ORCID ProfileRuth E. Ley
doi: https://doi.org/10.1101/2022.04.12.488020
Sara J. Clasen
1Department of Microbiome Science, Max Planck Institute for Biology, Tübingen 72076, Germany
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Michael E. W. Bell
1Department of Microbiome Science, Max Planck Institute for Biology, Tübingen 72076, Germany
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Du-Hwa Lee
2Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, Vienna, Austria
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Zachariah M. Henseler
1Department of Microbiome Science, Max Planck Institute for Biology, Tübingen 72076, Germany
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Andrea Borbón
1Department of Microbiome Science, Max Planck Institute for Biology, Tübingen 72076, Germany
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Jacobo de la Cuesta-Zuluaga
1Department of Microbiome Science, Max Planck Institute for Biology, Tübingen 72076, Germany
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Katarzyna Parys
2Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, Vienna, Austria
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Jun Zou
3Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA
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Nicholas D. Youngblut
1Department of Microbiome Science, Max Planck Institute for Biology, Tübingen 72076, Germany
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Andrew T. Gewirtz
3Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA
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Youssef Belkhadir
2Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, Vienna, Austria
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Ruth E. Ley
1Department of Microbiome Science, Max Planck Institute for Biology, Tübingen 72076, Germany
4Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, University of Tübingen, Tübingen, Germany
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  • For correspondence: ruth.ley@tuebingen.mpg.de
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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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 12, 2022.
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Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5
Sara J. Clasen, Michael E. W. Bell, Du-Hwa Lee, Zachariah M. Henseler, Andrea Borbón, Jacobo de la Cuesta-Zuluaga, Katarzyna Parys, Jun Zou, Nicholas D. Youngblut, Andrew T. Gewirtz, Youssef Belkhadir, Ruth E. Ley
bioRxiv 2022.04.12.488020; doi: https://doi.org/10.1101/2022.04.12.488020
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Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5
Sara J. Clasen, Michael E. W. Bell, Du-Hwa Lee, Zachariah M. Henseler, Andrea Borbón, Jacobo de la Cuesta-Zuluaga, Katarzyna Parys, Jun Zou, Nicholas D. Youngblut, Andrew T. Gewirtz, Youssef Belkhadir, Ruth E. Ley
bioRxiv 2022.04.12.488020; doi: https://doi.org/10.1101/2022.04.12.488020

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