title: Identification and functional characterization of chicken toll-like receptor 5 reveals a fundamental role in the biology of infection with Salmonella enterica serovar typhimurium.
abstract: 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-1beta (chIL-1beta) 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-1beta 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.
authors.affiliation: Division of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, United Kingdom.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Iqbal
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Philbin
authors.forename: G S K
authors.initials: GS
authors.lastname: Withanage
authors.forename: Paul
authors.initials: P
authors.lastname: Wigley
authors.forename: Richard K
authors.initials: RK
authors.lastname: Beal
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Goodchild
authors.forename: Paul
authors.initials: P
authors.lastname: Barrow
authors.forename: Ian
authors.initials: I
authors.lastname: McConnell
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.forename: John
authors.initials: J
authors.lastname: Young
authors.forename: Nat
authors.initials: N
authors.lastname: Bumstead
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Boyd
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D005408:Flagellin / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D005408:Flagellin