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Infection and Immunity, April 2005, p. 2344-2350, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2344-2350.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Identification and Functional Characterization of Chicken Toll-Like Receptor 5 Reveals a Fundamental Role in the Biology of Infection with Salmonella enterica Serovar Typhimurium{dagger}

Muhammad Iqbal,1 Victoria J. Philbin,1 G. S. K. Withanage,2 Paul Wigley,3 Richard K. Beal,1 Marianne J. Goodchild,4 Paul Barrow,3 Ian McConnell,2 Duncan J. Maskell,2 John Young,1 Nat Bumstead,4 Yvonne Boyd,4,{ddagger} and Adrian L. Smith1*

Divisions of Immunology and Pathology,1 Microbiology,3 Molecular Biology, Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire,4 Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom2

Received 8 October 2004/ Returned for modification 9 November 2004/ Accepted 10 December 2004

Toll-like receptors (TLRs) are a major component of the pattern recognition receptor repertoire that detect invading microorganisms and direct the vertebrate immune system to eliminate infection. In chickens, the differential biology of Salmonella serovars (systemic versus gut-restricted localization) correlates with the presence or absence of flagella, a known TLR5 agonist. Chicken TLR5 (chTLR5) exhibits conserved sequence and structural similarity with mammalian TLR5 and is expressed in tissues and cell populations of immunological and stromal origin. Exposure of chTLR5+ cells to flagellin induced elevated levels of chicken interleukin-1ß (chIL-1ß) but little upregulation of chIL-6 mRNA. Consistent with the flagellin-TLR5 hypothesis, an aflagellar Salmonella enterica serovar Typhimurium fliM mutant exhibited an enhanced ability to establish systemic infection. During the early stages of infection, the fliM mutant induced less IL-1ß mRNA and polymorphonuclear cell infiltration of the gut. Collectively, the data represent the identification and functional characterization of a nonmammalian TLR5 and indicate a role in restricting the entry of flagellated Salmonella into systemic sites of the chicken.

* Corresponding author. Mailing address: Enteric Immunology, Stewart Building G2D, Division of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, United Kingdom. Phone: 044 1635 577293. Fax: 044 1635 577263. E-mail: adrian.smith{at}bbsrc.ac.uk.

{dagger} We dedicate this article to the memory of our valued colleague and friend Nat Bumstead, who sadly passed away during the completion of this work.

Editor: F. C. Fang

{ddagger} Present address: TSE Research Unit, Science Directorate, Department of Environment Food and Rural Affairs, Westminster, London SW1P 3JH, United Kingdom.

Infection and Immunity, April 2005, p. 2344-2350, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2344-2350.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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