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Here, we screened abundant flagellins present in metagenomes from human gut for both TLR5 recognition and activation and uncovered a class of flagellin-TLR5 interaction termed silent recognition. Silent flagellins were weak TLR5 agonists despite pattern recognition. Receptor activity was tuned by a TLR5-flagellin interaction distal to the site of pattern recognition that was present in\n                    <jats:italic>Salmonella<\/jats:italic>\n                    flagellin but absent in silent flagellins. This interaction enabled flagellin binding to preformed TLR5 dimers and increased TLR5 signaling by several orders of magnitude. Silent recognition by TLR5 occurred in human organoids and mice, and silent flagellin proteins were present in human stool. These flagellins were produced primarily by the abundant gut bacteria Lachnospiraceae and were enriched in nonindustrialized populations. Our findings provide a mechanism for the innate immune system to tolerate commensal-derived flagellins while remaining vigilant to the presence of flagellins produced by pathogens.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.abq7001","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T16:04:47Z","timestamp":1674230687000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":118,"title":["Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2888-7040","authenticated-orcid":true,"given":"Sara J.","family":"Clasen","sequence":"first","affiliation":[{"name":"Department of Microbiome Science, Max Planck Institute for Biology, T\u00fcbingen 72076, 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