Diversity of gut commensal flagellins results in distinct intestinal epithelial cell immune responses

Abstract Flagellins from bacteria in the Lachnospiraceae family are immunodominant antigens inflammatory bowel disease. Flagellin is basic unit of flagella which used for bacterial motility and recognized by toll-like receptor 5 (TLR5). Due to diversity flagellated organisms that reside proximity intestinal epithelium, we asked whether this resulted distinct interactions between commensal flagellins immune system. Analysis over 200 flagellins, primarily organisms, revealed a divergence peptide sequences specific non-conserved regions D0 domain broadly separate examined into 2 clusters refer as Group 1 flagellins. We stimulated HEK-Blue mTLR5 cells murine epithelial (IECs) with selected or assess TLR5 activity IEC production lipocalin-2 (Lcn-2) - biomarker inflammation respectively. flagellin strongly activated signaling HEK cell line, even more so than Salmonella typhimurium (S. typhi) flagellin. Conversely, exhibited significantly reduced relative both S. typhi While stimulation undetectable Lcn-2, led robust Lcn-2 production; These findings demonstrate elicit differential response via selective activation TLR5. functional differences dependent on motifs their domains. Supported R01 AI162736, R21 DK118386, T32 AI007051.