RT Journal Article
SR Electronic
T1 Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.12.488020
DO 10.1101/2022.04.12.488020
A1 Sara J. Clasen
A1 Michael E. W. Bell
A1 Du-Hwa Lee
A1 Zachariah M. Henseler
A1 Andrea Borbón
A1 Jacobo de la Cuesta-Zuluaga
A1 Katarzyna Parys
A1 Jun Zou
A1 Nicholas D. Youngblut
A1 Andrew T. Gewirtz
A1 Youssef Belkhadir
A1 Ruth E. Ley
YR 2022
UL http://biorxiv.org/content/early/2022/04/12/2022.04.12.488020.abstract
AB 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 StatementThe authors have declared no competing interest.