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Cutting Edge: FimH Adhesin of Type 1 Fimbriae Is a Novel TLR4 Ligand¹

Karen L. Mossman^*, M. Firoz Mian^*, Nicole M. Lauzon^*, Carlton L. Gyles, Brian Lichty^*, Randy Mackenzie^*, Navkiran Gill^* and Ali A. Ashkar^2,*

^* Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; and Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada

Several TLR ligands of bacterial origin induce innate immune responses. Although FimH, the adhesin portion of type 1 fimbria, plays an important role in the pathogenicity of some Gram-negative bacteria, its ability to stimulate the innate immune system via TLR signaling remains unclear. In this study we report that FimH induces potent innate responses in a MyD88-dependent fashion. The FimH-induced innate activity was restricted to cells expressing TLR4. In addition, FimH was able to bind directly to TLR4. More importantly, cells unresponsive to LPS were responsive to FimH and the presence or absence of MD-2 and CD14 had no effect on FimH activity. Our data suggest that TLR4 is a functional receptor for the adhesin portion of bacterial type 1 fimbria.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Canadian Institutes of Health Research and the Hospital for Sick Children Foundation to A.A.A. and from Canadian Institutes of Health Research to K.L.M.

² Address correspondence and reprint requests to Dr. Ali A. Ashkar, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5. E-mail address: ashkara{at}mcmaster.ca

³ Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; B6, C57BL/6; HEL, human embryonic fibroblast; hTLR4, human TLR4; MEF, murine embryonic fibroblast; poly(I:C), polyinosinic:polycitidylic acid; UPEC, uropathogenic E. coli; VSV, vesicular stomatitis virus.

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