FUNCTIONAL GENOMICS AND GENETIC ANALYSIS OF THE INNATE IMMUNE RESPONSE REQUIRED TO RESIST FOOD-BORNE BACTERIAL INFECTIONS IN POULTRY
Location: Food and Feed Safety Research
Title: Dynamics of the avian inflammatory response to Salmonella following administration of the toll-like receptor 5 agonist flagellin
Submitted to: FEMS Immunology and Medical Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 17, 2007
Publication Date: July 19, 2007
Citation: Genovese, K.J., He, H., Lowry, V.K., Nisbet, D.J., Kogut, M.H. 2007. Dynamics of the avian inflammatory response to Salmonella following administration of the toll-like receptor 5 agonist flagellin. FEMS Immunology and Medical Microbiology. 51(1):112-117.
Interpretive Summary: This study describes the use of a bacterial-derived protein, flagellin, as an immune-stimulatory agent in chickens. Chickens were given the flagellin as an injection into their abdomen. One hour later, chickens were then given an abdominal injection of Salmonella bacteria. Following the injection of Salmonella, blood was collected at different time points and the number and types of white blood cells were counted. Cells moving into the abdomen were also counted and typed. In addition, mortality was compared between flagellin-treated and untreated chickens after an abdominal injection of Salmonella bacteria. The results of these studies indicate that flagellin caused an increase in white blood cells in the circulating blood supply and in the abdomen. The primary cell accounting for the increase in white blood cells both in the abdomen and in the circulating blood was the heterophil. Flagellin injection also reduced mortality associated with Salmonella injection by 50%. In conclusion, flagellin stimulates the chicken's immune system and in doing so, protects chickens from Salmonella-associated mortality.
Flagellin is a highly evolutionarily conserved bacterial component that is recognized by the innate immune system through toll-like receptor (TLR) 5. Previous work has shown that flagellin is a potent stimulator in vitro of phagocytic cell functions of chickens. The purpose of the present study was to define the effects of flagellin administration on the avian inflammatory response to Salmonella in chickens. Chicks administered an intra-abdominal (IA) injection of flagellin had significantly (P less than or equal to 0.05) increased peripheral white blood cells (PWBC) compared to saline-injected control birds and Salmonella-injected birds at 4, 8, and 24hr post-injection (P less than or equal to 0.05). In addition, IA white blood cell infiltrates (IWBC) were significantly higher in the flagellin-injected birds compared to saline- and Salmonella-injected birds (P less than or equal to 0.05). In both the peripheral blood and in the abdominal cavity, the predominant leukocyte accounting for the increases observed in cell numbers was the heterophil (P less than or equal to 0.05). IA injection of flagellin was also found to reduce Salmonella-associated mortality by 50% compared to mortality observed in the Salmonella-injected control groups (P less than or equal to 0.05). The data suggest that the TLR 5 agonist, flagellin, is also a potent stimulator of a heterophil-mediated innate immune response in vivo, with subsequent protective induction of an inflammatory response to bacterial infections in the chicken.