Dynamics of the avian inflammatory response toSalmonellafollowing administration of the toll-like receptor 5 agonist flagellin

Abstract

Previous work has shown that flagellin (FGN) is a potent stimulator in vitro of phagocytic cell functions of chickens. The purpose of this study was to define the effects of FGN on the inflammatory response to Salmonella enteritidis (SE) in chickens. Intraabdominal (IA) FGN administration caused significant increases in peripheral blood leukocytes (PBL) compared with SE-injected controls at 4 and 8 h postinjection (P 0.05). The heterophil (PMN) was the predominant cell responsible for the increased numbers of leukocytes in the peripheral blood. In the abdominal cavity, leukocyte infiltrates were significantly greater in FGN-injected (8 h) and SE/FGNinjected (4 and 24 h) birds than in the SE-injected control birds. Again, the predominant leukocyte infiltrating the abdominal cavity was the PMN. Bovine serum albumin (BSA)-injected protein control birds showed no increases in PBL or in abdominal cell leukocyte infiltrates over saline-injected controls. In IA challenge studies, FGN reduced SE-associated mortality (26%) compared with mortality of 51% in the SE group (P 0.05). BSA-injected/SE-challenged chicks had mortality similar to that of the SE group. The data suggest that FGN is a potent stimulator of a heterophil-mediated innate immune response in vivo, protecting against bacterial infections in chickens.

Flagellin: key target of mucosal innate immunity

“…45 Exogenous administration of flagellin also protected against systemic Salmonella infection in both mice and chickens. 46,47 Kumar et al 48 showed that the administration of Pseudomonas aeruginosa flagellin through the subconjunctival and intraperitoneal routes 24 h before Pseudomonas infection reduced inflammatory pathology in a mouse model of P. aeruginosa -induced keratitis. 48 Finally, prophylactic administration of flagellin to mice made them resistant to rotavirus infection.…”

Modulation of Chicken Intestinal Immune Gene Expression by Small Cationic Peptides as Feed Additives during the First Week Posthatch

“…We have targeted the innate immune responses for the development of immunomodulatory and/or antimicrobial compounds for prevention or treatment of bacterial infections in neonatal poultry (2,3,(13)(14)(15)(16)(17). Since the innate immune response is not pathogen specific, the ability to stimulate the response in birds is a promising approach of increasing resistance to a variety of pathogens.…”

“…Since the innate immune response is not pathogen specific, the ability to stimulate the response in birds is a promising approach of increasing resistance to a variety of pathogens. The one characteristic of the avian innate response that we have exploited is the ability of the response to be modulated during the first week after hatch (3,15,18,19). We have shown that the stimulated response results in an increased resistance to Salmonella infections with concomitant increases in heterophil functional activity (2,3,(13)(14)(15)(16)(17).…”

Flagellin A Toll-Like Receptor 5 Agonist as an Adjuvant in Chicken Vaccines

“…In this regard, flagellin administered in vivo enhanced the infiltration of heterophils into the site of injection, which suggests that flagellin is a potent stimulator of a heterophil-mediated innate immune response in vivo and can protect against Salmonella infections in chickens (81). Although the exact mechanism behind this phenomenon was not clearly documented, it was reasoned to be mediated by the TLR5-flagellin-induced production chemotactic factor IL-8 (76).…”

“…Flagellin has emerged as a potential adjuvant candidate for vaccines due to a number of advantages associated with it. It has been shown to be effective at very low doses (81,82), and previous immunity does not alter its adjuvant activity, as it has high affinity for TLR5 (95,96). Being protein in nature, it can be manipulated and epitopes can be fused with its N or C terminus as well as in the (99).…”