This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Iqbal, M. Articles by Smith, A. L. Search for Related Content PubMed PubMed Citation Articles by Iqbal, M. Articles by Smith, A. L.

 Previous Article  |  Next Article 

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

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, and Adrian L. Smith^1*

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.

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

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

This article has been cited by other articles:

• Keestra, A. M., van Putten, J. P. M. (2008). Unique Properties of the Chicken TLR4/MD-2 Complex: Selective Lipopolysaccharide Activation of the MyD88-Dependent Pathway. J. Immunol. 181: 4354-4362 [Abstract] [Full Text]  
• Lillehoj, H. S., Kim, C. H., Keeler, C. L. Jr., Zhang, S. (2007). Immunogenomic Approaches to Study Host Immunity to Enteric Pathogens. Poult. Sci. 86: 1491-1500 [Abstract] [Full Text]  
• Keestra, A. M., de Zoete, M. R., van Aubel, R. A. M. H., van Putten, J. P. M. (2007). The Central Leucine-Rich Repeat Region of Chicken TLR16 Dictates Unique Ligand Specificity and Species-Specific Interaction with TLR2. J. Immunol. 178: 7110-7119 [Abstract] [Full Text]  
• Adriaensen, C., De Greve, H., Tian, J. Q., De Craeye, S., Gubbels, E., Eeckhaut, V., Van Immerseel, F., Ducatelle, R., Kumar, M., Hernalsteens, J.-P. (2007). A Live Salmonella enterica Serovar Enteritidis Vaccine Allows Serological Differentiation between Vaccinated and Infected Animals. Infect. Immun. 75: 2461-2468 [Abstract] [Full Text]  
• Vijay-Kumar, M., Wu, H., Jones, R., Grant, G., Babbin, B., King, T. P., Kelly, D., Gewirtz, A. T., Neish, A. S. (2006). Flagellin Suppresses Epithelial Apoptosis and Limits Disease during Enteric Infection. Am. J. Pathol. 169: 1686-1700 [Abstract] [Full Text]  
• Higgs, R., Cormican, P., Cahalane, S., Allan, B., Lloyd, A. T., Meade, K., James, T., Lynn, D. J., Babiuk, L. A., O'Farrelly, C. (2006). Induction of a Novel Chicken Toll-Like Receptor following Salmonella enterica Serovar Typhimurium Infection. Infect. Immun. 74: 1692-1698 [Abstract] [Full Text]