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

<jats:title>ABSTRACT</jats:title> <jats:p>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 <jats:italic>Salmonella</jats:italic> 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<jats:sup>+</jats:sup> cells to flagellin induced elevated levels of chicken interleukin-1β (chIL-1β) but little upregulation of chIL-6 mRNA. Consistent with the flagellin-TLR5 hypothesis, an aflagellar <jats:italic>Salmonella enterica</jats:italic> serovar Typhimurium <jats:italic>fliM</jats:italic> mutant exhibited an enhanced ability to establish systemic infection. During the early stages of infection, the <jats:italic>fliM</jats:italic> mutant induced less IL-1β 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 <jats:italic>Salmonella</jats:italic> into systemic sites of the chicken.</jats:p>