Although passively-administered hyperimmune serum conferred protection in intact birds [15,17,18], the contribution of innate defenses and cell-mediated immunity to the control of APEC in the avian host remains ill-defined

Although passively-administered hyperimmune serum conferred protection in intact birds [15,17,18], the contribution of innate defenses and cell-mediated immunity to the control of APEC in the avian host remains ill-defined. poultry and exert significant economic and welfare costs. Infections are frequently associated with sudden death, salpingitis, peritonitis, pericarditis, perihepatitis, airsacculitis and with reduced yield, quality and hatching of eggs. Analysis of the repertoire of virulence-associated genes among APEC has indicated LTI-291 that some strains are closely related to causing human extraintestinal infections, in particular uropathogenic and neonatal meningitis-causing infections, the onset of sexual maturity and stress associated with sub-optimal husbandry practices are leading antecedents to colibacillosis in farmed poultry. Despite improvements in poultry production systems over the years, APEC continue to pose a formidable challenge to poultry farmers, threatening food security at a time of increasing global demand. The expansion of free-range production systems in Europe and elsewhere may be expected to increase the incidence of colibacillosis owing to greater exposure of farmed birds to environmental pathogens, stress and injury associated with formation of a social hierarchy. Indeed, in field surveys colibacillosis was the most common bacterial infection in birds reared free-range (with cases peaking between onset of lay and 30?weeks of age) and a positive correlation between vent-pecking and the incidence of colibacillosis was reported [5,6]. Systemic APEC infections are believed to arise from colonisation of the lower respiratory tract following inhalation of contaminated faecal dust, where levels can reach up to 106 viable per gram in poultry houses [7]. Colonisation of the airsacs is enhanced by suppression of muco-ciliary activity and other upper respiratory tract defences resulting from concurrent infections and elevated ammonia levels in poultry houses. Avian airsacs are relatively avascular structures lacking effective resident defence mechanisms [8], hence control of pathogens is thought to be reliant upon recruitment of heterophils and macrophages [9]. The mode of translocation of APEC from the respiratory tract to the bloodstream is ill-defined. APEC can be found in the bloodstream as early as 3?hours after intra-airsac inoculation of na?ve birds [10,11], and the immune responses that constrain such spread are unclear. Systemic spread of APEC may be followed by sepsis or localised inflammation in survivors involving extensive heterophil infiltration in organs of the reticulo-endothelial system [12-14]. Prophylactic use of antibiotics to control APEC in poultry is restricted owing to the risk of residues entering the food chain and the potential for the evolution of multi-drug resistant strains. Vaccination offers an attractive route to control APEC and inactivated and live-attenuated vaccines are commercially available. Autologous bacterins are effective but confer serogroup-specific protection and are believed to act principally through induction of humoral responses. The serogroup-specificity of such vaccines has been inferred to be due to the dominance of responses to the lipopolysaccharide O antigen. As avian colibacillosis is caused by multiple APEC serotypes, a requirement exists for broadly cross-protective vaccines. Earlier studies indicate that LTI-291 live-attenuated APEC vaccines or a low dose of virulent APEC confer a higher degree of cross-serogroup protection compared to killed vaccines [15,16], however, the immunological basis of protection has not been properly dissected. Although passively-administered hyperimmune serum conferred protection in intact birds [15,17,18], the contribution of innate defenses and cell-mediated immunity to the control of APEC in the avian host remains ill-defined. A better understanding of the nature and consequences of avian responses MLNR to APEC infection, and their association with recovery from primary infection and protection against re-challenge, can LTI-291 be expected to inform the rational design of control strategies. In this study, we developed a model of sub-acute APEC O78:H9 infection in turkey poults and examined cytokine and antigen-specific cell-mediated and humoral responses prior to and after homologous re-challenge. Materials and methods Bacterial strains, media and growth conditions APEC strain derivative of for the duration of the experiment. Primary and secondary infection with APEC strain and DNA polymerase during.