Salmonella Immunobiology and Intervention Strategies

Salmonella enteritidis (SE) carried by chickens and shed into and onto shell eggs has become a major source of human intestinal infections. Despite a large amount of research, there are still no effective measures for preventing SE colonization, and we still lack an understanding of why Salmonella infected hens remain persistently infected. This study will investigate the immunobiology of Salmonella infections in laying chickens and develop novel immunomodulating strategies for the intervention of Salmonella colonization, persistence, shedding and egg contamination.
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The immune system is still the most powerful and effective system the host has in preventing and eliminating infections by microorganisms. Although SE infection may not result in serious illness in chickens, a carrier state may be established, suggesting that the immune system of the chicken is ineffective in completely preventing SE infection, invasion and shedding. We propose to systematically examine the immune system of the chicken before, during and after SE infection to gain a greater understanding of how the microorganism and the immune system interact. We will also examine mechanisms of altering this immune response in order to enhance the resistance to colonization, enhance the elimination of the microorganism and prevent shedding. Studies will not only take place under controlled laboratory conditions, but will also investigate the impact of the immune system on Salmonella infections of commercial laying chickens on farms. In recent years, SE has been the most commonly isolated Salmonella serotype in humans in the U.S.6 Between 1985 and 1991, eggs were the primary vehicle of SE infection in 82% of human food borne outbreaks.7 Control of SE in man will depend upon effective means of reducing SE in eggs. In order to effectively do this we must first understand the pathogenesis of Salmonella in poultry and the impact the immune system has on this infection. This could lead to strategies to modulate the immune system to better prevent and control Salmonella infections, thereby leading to effective pathogen reduction or elimination. We have established a consortium of researchers with expertise relevant to addressing the above research goals. This group will carry out a comprehensive evaluation of the role of the immune system in SE-elimination from various age groups of birds. In this proposal, we will investigate the potential of several intervention strategies for controlling SE infection in hens and determine their possible mechanisms of action. Additionally, the field component of this proposal is a unique feature, which has been identified as a key factor in the egg safety action plan (a federal initiative designed to reduce the threat of SE in shell eggs). Our proposed work includes examining the impact of forced molting on the immune system and SE in commercial laying hens. We have performed preliminary studies on various aspects of Salmonella-host interaction and have established the methodology necessary to carry out the investigations outlined in this proposal. This research should not only provide basic information on the pathogen-host cell interaction, but also give vital information on how the immune system of the chicken can be used to control or eliminate the spread of SE from animals to man.
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Overall, the results of this grant showed that oral vaccination with live attenuated SE vaccine enhanced cell mediated immunity with increased SE clearance. However, killed vaccine enhanced the humoral immune response with no impact on the SE clearance. CpG oligonucleotides were shown to be efficacious in poultry and can be used to modulate the immune response. When given with killed vaccines CpG oligoneucleotides were shown to increase the resistance to infection if given parenterally or in ovo. These results suggest that vaccination with attenuated live Salmonella could be an effective method for controlling Salmonella enteritidis infection in young chickens.
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Better methods of affecting Salmonella infection or persistence of infection in laying hens may lead to decreased on-farm Salmonella prevalence and therefore potentially less human food borne illness.