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Title:   Author  item
                                            Lillehoj, Hyun
  Submitted to: Workshop Proceedings
                                    Publication Type: Proceedings
                                    Publication Acceptance Date: 10/17/2006
                                    Publication  Date: 12/3/2006
                                    Citation: Lillehoj, H.S. 2006. Identification of protective innate immune mechanisms in coccidiosis and salmonellosis. Proceedings of CSREES NRI Project Leader Meeting. Dec 3, Chicago, IL.Interpretive Summary: This is a CSREES NRI-funded project report for 2006. Two-year NRICGP USDA-funded project was started in September, 2004 to develop new strategies to reduce economic losses due to salmonellosis and coccidiosis.  The short-term goals of this proposal included expanding our basic understanding of the function of macrophages in avian salmonellosis and coccidiosis and  investigation of the underlying innate immune mechanisms associated with the intracellular killing of Salmonella and Eimeria.  In this project, we explored high throughput gene expression profiling tools using newly developed chicken macrophage and intestinal cDNA microarraies to identify the host genes which control innate immune responses to enteric intracellular pathogens.  The report demonstrates that we have identified several important macrophage genes which are activated during the early phase of immune response to three major Eimeria infections. Further characterization of these innate immunity genes will facilitate the development of novel strategy against cocccidiosis and salmonellosis.
                                Technical Abstract: A major stumbling block in the development of novel control strategy against many mucosal poultry pathogens in poultry is the lack of comprehensive understanding of how host immune system interact and how protective immunity develops against mucosal pathogens. For example, in coccidiosis and salmonellosis which are the major intestinal  diseases of poultry of economic importance, increasing evidences indicate the complexity of the host immune responses involving many effector cell types and cytokines in response to Eimeria and Salmonella. In this project, new tissue specific chicken microarrays (macrophage and intestine) were used to examine global gene expression induced by Eimeria and Salmonella.  Using an avian macrophage microarray containing 4,906 unique gene elements, we identified important host genes whose expression changed following infection of macrophages with sporozoites of E. tenella, E. acervulina, and E. maxima.  This approach enabled us to identify a common core of 25 genetic elements whose transcriptional expression is induced or repressed by exposure to Eimeria sporozoites and to identify additional transcription patterns unique to each individual Eimeria species.  Besides inducing the expression of IL 1, IL 6, and IL 18 and repressing the expression of IL 16, Eimeria treated macrophages were commonly found to induce the expression of the CCL chemokine family members MIP 1 (CCLi1), K203 (CCLi3), and ah221 (CCLi7).  Fundamental analysis of avian chemokine and cytokine expression patterns offers insight into the unique avian immunological responses to these related but biologically unique pathogens. Recently molecular changes in immune related macrophage genes following infection of chicken macrophages with Salmonella have been evaluated and the results are being analyzed. Determining which macrophage genes are transcribed during the early stages of Eimeria and Salmonella infections will enhance our understanding of the molecular pathogenesis of coccidiosis and salmonellosis.  This study also shows that early macrophage activation events induced by individual species of Eimeria appears to correlate with the number of genes and the overall magnitude of the transcriptional response elicited by each individual species.  Such differential responses may be attributed to the species specific immunity induced by each Eimeria sp. and a deeper look into the functional aspects of those elements could prove critical in shedding some light on the lack of cross species protection. Further characterization of both sets of elements would help elucidate the pathogenicity and/or immunogenicity of these pathogens leading to better recombinant vaccine design and control strategies against coccidiosis and salmonellosis.


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