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

• Published in: Infection and Immunity 2005-04, Vol.73 (4), p.2344-2350
• Main Authors: Iqbal, Muhammad, Philbin, Victoria J, Withanage, G. S. K, Wigley, Paul, Beal, Richard K, Goodchild, Marianne J, Barrow, Paul, McConnell, Ian, Maskell, Duncan J, Young, John, Bumstead, Nat, Boyd, Yvonne, Smith, Adrian L
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Chickens; Flagellin - metabolism; Host Response and Inflammation; Interleukin-1 - genetics; Interleukin-6 - genetics; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Molecular Sequence Data; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - genetics; Receptors, Cell Surface - physiology; RNA, Messenger - analysis; Salmonella enterica; Salmonella Infections, Animal - immunology; Salmonella typhimurium - immunology; Toll-Like Receptor 5; Toll-Like Receptors
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.73.4.2344-2350.2005

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-1{szligbeta} (chIL-1{szligbeta}) 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-1{szligbeta} 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.