Molecular Immunology 44 (2007) 558–566 Unique responses of the avian macrophage to different species of Eimeria Rami A. Dalloul a,1 , Travis W. Bliss b,1 , Yeong-Ho Hong a , Imed Ben-Chouikha a , Dong Woon Park a , Calvin L. Keeler b , Hyun S. Lillehoj a,∗ a Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, USDA Agricultural Research Service, Bldg. 1040, BARC-East, Beltsville, MD 20705, United States b Department of Animal and Food Sciences, College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19716, United States Received 6 January 2006; received in revised form 7 February 2006; accepted 9 February 2006 Available online 24 March 2006 Abstract Coccidiosis is recognized as the major parasitic disease of poultry and is caused by the apicomplexan protozoa Eimeria. Increasing evidence shows the complexity of the host immune response to Eimeria and microarray technology presents a powerful tool for the study of such an intricate biological process. Using an avian macrophage microarray containing 4906 unique gene elements, we identified important host genes whose expression changed following infection of macrophages with sporozoites of Eimeria tenella (ET), Eimeria acervulina (EA), and Eimeria maxima (EM). 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 macrophage inflammatory protein (MIP)-1 (CCLi1), K203 (CCLi3), and ah221 (CCLi7). However, the CXCL chemokine K60 (CXCLi1) was found to be induced by macrophage exposure to E. tenella but was repressed upon macrophage exposure to E. maxima and E. acervulina. Fundamental analysis of avian chemokine and cytokine expression patterns offers insight into the unique avian immunological responses to these related but biologically unique pathogens. © 2006 Elsevier Ltd. All rights reserved. Keywords: Macrophage; Eimeria; cDNA microarray; Cytokines; Chemokines; Coccidia; Immunology; Chicken 1. Introduction Coccidiosis is recognized as the major parasitic disease of poultry and is caused by the apicomplexan protozoa Eimeria. Coccidiosis seriously impairs the growth and feed utilization of infected birds resulting in loss of productivity and it inflicts economic losses in excess of US $3 billion annually to the world poultry industry (Shirley et al., 2004; Williams, 1999). Conventional disease control strategies rely heavily on chemo- prophylaxis and to a certain extent on live vaccines (Dalloul and Lillehoj, 2005). Increasing regulations and bans on the use of Abbreviations: AMM, avian macrophage microarray; FDR, false discovery rate; Q-RT-PCR, quantitative real time reverse-transcriptase polymerase chain reaction ∗ Corresponding author. Tel.: +1 301 504 6170; fax: +1 301 504 5103. E-mail address: hlilleho@anri.barc.usda.gov (H.S. Lillehoj). 1 These authors contributed equally to this work. anticoccidial drugs coupled with the associated costs for devel- oping new drugs and live vaccines has stimulated the need for developing novel approaches and alternative control strategies for coccidiosis. However, such new approaches will only be real- ized after a systematic and detailed analysis of host–parasite interactions at the molecular and cellular levels are completed. In particular, fundamental knowledge of the basic immunobiol- ogy from initial parasite invasion to intracellular development and ultimate elimination from the host is very limited. Increas- ing evidence demonstrates the complexity of the host immune responses to Eimeria. Additional basic research is needed to ascertain the detailed immunological and physiological pro- cesses mediating protective immunity. Chickens have evolved a sophisticated immune system where macrophages play significant roles in both the innate and acquired immune responses. As in mammals, avian macrophages act as antigen presenting cells for B and T lymphocytes and stimulate the activation of other immune 0161-5890/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.molimm.2006.02.004