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

TLDR

Toll‑like receptor 5 in chickens recognizes bacterial flagellin and, like its mammalian counterpart, is expressed in immune and stromal tissues, providing a key innate immune sensor that distinguishes flagellated from aflagellated Salmonella serovars. Activation of chicken TLR5 by flagellin triggers IL‑1β production, and loss of flagellin in a Salmonella Typhimurium fliM mutant leads to increased systemic infection and reduced early gut inflammation, demonstrating that chTLR5 limits flagellated Salmonella dissemination.

Abstract

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-1β (chIL-1β) 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-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 Salmonella into systemic sites of the chicken.