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Brief Report

Bacterial flagellin is a dominant, stable innate immune activator in the gastrointestinal contents of mice and rats

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Article: 2185031 | Received 12 Sep 2022, Accepted 21 Feb 2023, Published online: 07 Mar 2023

References

  • Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533. doi:10.1371/journal.pbio.1002533.
  • Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara JL. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. Eur J Immunol. 2001;167(4):1882–10. doi:10.4049/jimmunol.167.4.1882.
  • Raby AC, Le Bouder E, Colmont C, Davies J, Richards P, Coles B, George CH, Jones SA, Brennan P, Topley N, et al. Soluble TLR2 reduces inflammation without compromising bacterial clearance by disrupting TLR2 triggering. Eur J Immunol. 2009;183(1):506–517. doi:10.4049/jimmunol.0802909.
  • Zunt SL, Burton LV, Goldblatt LI, Dobbins EE, Srinivasan M. Soluble forms of toll-like receptor 4 are present in human saliva and modulate tumour necrosis factor-α secretion by macrophage-like cells. Clin Exp Immunol. 2009;156(2):285–293. doi:10.1111/j.1365-2249.2009.03854.x.
  • LeBouder E, Rey-Nores JE, Rushmere NK, Grigorov M, Lawn SD, Affolter M, Griffin GE, Ferrara P, Schiffrin EJ, Morgan BP, et al. Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk. Eur J Immunol. 2003;171(12):6680–6689. doi:10.4049/jimmunol.171.12.6680.
  • Gewirtz AT, Simon PO Jr., Schmitt CK, Taylor LJ, Hagedorn CH, O’brien AD, Neish AS, Madara JL. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J Clin Invest. 2001;107(1):99–109. doi:10.1172/JCI10501.
  • Lyons S, Wang L, Casanova JE, Sitaraman SV, Merlin D, Gewirtz AT. Salmonella typhimurium transcytoses flagellin via an SPI2-mediated vesicular transport pathway. J Cell Sci. 2004;117(24):5771–5780. doi:10.1242/jcs.01500.
  • Hoshi N, Schenten D, Nish SA, Walther Z, Gagliani N, Flavell RA, Reizis B, Shen Z, Fox JG, Iwasaki A, et al. MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nat Commun. 2012;3(1):1120. doi:10.1038/ncomms2113.
  • Smith KD, Andersen-Nissen E, Hayashi F, Strobe K, Bergman MA, Barrett SL, Cookson BT, Aderem A. Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat Immunol. 2003;4(12):1247–1253. doi:10.1038/ni1011.
  • Guo S, Al-Sadi R, Said HM, Ma TY. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol. 2013;182(2):375–387. doi:10.1016/j.ajpath.2012.10.014.
  • Galloway SM, Raetz CR. A mutant of escherichia coli defective in the first step of endotoxin biosynthesis. J Biol Chem. 1990;265(11):6394–6402. doi:10.1016/S0021-9258(19)39339-1.
  • Murphy ST, Bellamy MC. The quest for the magic bullet: centoxin, drotrecogin alfa and lessons not learned. Trends Anaesth Crit. 2013;3(6):316–319. doi:10.1016/j.tacc.2013.05.004.
  • Rice TW, Wheeler AP, Bernard GR, Vincent J-L, Angus DC, Aikawa N, Demeyer I, Sainati S, Amlot N, Cao C, et al. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med. 2010;38(8):1685–1694. doi:10.1097/CCM.0b013e3181e7c5c9.
  • Opal SM, Laterre PF, Francois B, LaRosa SP, Angus DC, Mira JP, Wittebole X, Dugernier T, Perrotin D, Tidswell M, et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. Jama. 2013;309(11):1154–1162. doi:10.1001/jama.2013.2194.
  • d’Hennezel E, Abubucker S, Murphy LO, Cullen TW, Lozupone C. Total lipopolysaccharide from the human gut microbiome silences toll-like receptor signaling. mSystems. 2017; 2(6). doi:10.1128/mSystems.00046-17.
  • Vatanen T, Kostic AD, d’Hennezel E, Siljander H, Franzosa EA, Yassour M, Kolde R, Vlamakis H, Arthur T, Hämäläinen A-M, et al. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell. 2016;165(4):842–853. doi:10.1016/j.cell.2016.04.007.
  • Lozupone C, Faust K, Raes J, Faith JJ, Frank DN, Zaneveld J, Gordon JI, Knight R. Identifying genomic and metabolic features that can underlie early successional and opportunistic lifestyles of human gut symbionts. Genome Res. 2012;22(10):1974–1984. doi:10.1101/gr.138198.112.
  • Alexander KL, Zhao Q, Reif M, Rosenberg AF, Mannon PJ, Duck LW, Elson CO. Human microbiota flagellins drive adaptive immune responses in crohn’s disease. Gastroenterology. 2021;161(2):522–35 e6. doi:10.1053/j.gastro.2021.03.064.
  • Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, Fort M, Hershberg RM. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest. 2004;113(9):1296–1306. doi:10.1172/JCI200420295.
  • Gewirtz AT, Vijay-Kumar M, Brant SR, Duerr RH, Nicolae DL, Cho JH. Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn’s disease. Am J Physiol Gastrointest Liver Physiol. 2006;290(6):G1157–63. doi:10.1152/ajpgi.00544.2005.
  • Scheithauer TPM, Herrema H, Yu H, Bakker GJ, Winkelmeijer M, Soukhatcheva G, Dai D, Ma C, Havik SR, Balvers M, et al. Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction. Gut Microbes. 2022;14(1):2111951. doi:10.1080/19490976.2022.2111951.
  • Zhang B, Chassaing B, Shi Z, Uchiyama R, Zhang Z, Denning TL, Crawford SE, Pruijssers AJ, Iskarpatyoti JA, Estes MK, et al. Prevention and cure of rotavirus infection via TLR5/NLRC4–mediated production of IL-22 and IL-18. Science. 2014;346(6211):861–865. doi:10.1126/science.1256999.
  • Jones RM, Sloane VM, Wu H, Luo L, Kumar A, Kumar MV, Gewirtz AT, Neish AS. Flagellin administration protects gut mucosal tissue from irradiation-induced apoptosis via MKP-7 activity. Gut. 2011;60(5):648–657. doi:10.1136/gut.2010.223891.
  • Vijay-Kumar M, Aitken JD, Sanders CJ, Frias A, Sloane VM, Xu J, Neish AS, Rojas M, Gewirtz AT. Flagellin treatment protects against chemicals, bacteria, viruses, and radiation. Eur J Immunol. 2008;180(12):8280–8285. doi:10.4049/jimmunol.180.12.8280.
  • Vijay-Kumar M, Wu H, Jones R, Grant G, Babbin B, King TP, Kelly D, Gewirtz AT, Neish AS. Flagellin suppresses epithelial apoptosis and limits disease during enteric infection. Am J Pathol. 2006;169(5):1686–1700. doi:10.2353/ajpath.2006.060345.
  • Burdelya LG, Krivokrysenko VI, Tallant TC, Strom E, Gleiberman AS, Gupta D, Kurnasov OV, Fort FL, Osterman AL, Didonato JA, Feinstein, E, Gudkov, AV, et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science. 2008;320(5873):226–230. doi:10.1126/science.1154986.