Identification and functional characterization of chicken toll-like receptor 5 reveals a fundamental role in the biology of infection with Salmonella enterica serovar typhimurium.
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.
Iqbal
Muhammad
M
Division of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, United Kingdom.
Philbin
Victoria J
VJ
Withanage
G S K
GS
Wigley
Paul
P
Beal
Richard K
RK
Goodchild
Marianne J
MJ
Barrow
Paul
P
McConnell
Ian
I
Maskell
Duncan J
DJ
Young
John
J
Bumstead
Nat
N
Boyd
Yvonne
Y
Smith
Adrian L
AL
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
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