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Title:   Author  item
                                            Kim, Duk Kyungitem
                                            Lillehoj, Hyunitem
                                            MIN, WONGI - Gyeongsang National Universityitem
                                            KIM, CHUL HONG - Non ARS Employeeitem
                                            PARK, MYEONG SEON - Non ARS Employeeitem
                                            HONG, YEONG HO - Chung-Ang Universityitem
                                            LILLEHOJ, ERIC - University Of Maryland
  Submitted to: PLOS ONE
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/15/2012
                                    Publication  Date: 6/25/2012
                                    Citation: Kim, D., Lillehoj, H.S., Min, W., Kim, C., Park, M., Hong, Y., Lillehoj, E. 2012. Comparative microarray analysis of intestinal lymphocytes following Eimeria acervulina, E. maxima, or E. tenella infection in the chicken. PLoS One. 6(11). DOI: 10.1371/journal.pone.0027712.Interpretive Summary: Avian coccidiosis is caused by seven species of Eimeria protozoa that differ in pathogenicity and immunogenicity.  The life cycles of all Eimeria species are of the monoxenous sporozoan type.  Generally, infection develops following ingestion of sporulated oocysts and release of sporozoites, which subsequently invade intestinal epithelial cells.  Through asexual reproduction, gametes are formed and fertilized to produce a zygote, which matures into an oocyst, ruptures the host cell, and is excreted in the feces.  Eimeria infection inflicts significant economic losses to the commercial poultry industry.  Although prophylactic chemotherapy has been traditionally used for disease control, the emergence of drug-resistant parasites and legislative bans on the use of in-feed antibiotic growth promoters and non-therapeutic antimicrobial feed additives encourages the development of alternative coccidiosis control strategies.  Accordingly, there has been great interest in understanding the host-pathogen interactions at the cellular and molecular levels and to identify effector molecules mediating protective immunity to Eimeria. 
This study describes the transcriptional responses of chicken intestinal lymphocytes following in vivo experimental infection with E. acervulina, E. maxima, or E. tenella using the AVIELA microarray.  Biological function and pathway analysis identified the altered transcripts being relevant to lipid metabolism, as well as cellular and humoral immunity.  These new developments further enhance our understanding of the host response to Eimeria infection that may someday contribute to the development of the alternative control strategies against avian coccidiosis whose treatment has traditionally relied upon prophylactic medication and antibiotics.
                                Technical Abstract: Relative expression levels of immune- and non-immune-related mRNAs in chicken intestinal intraepithelial lymphocytes experimentally infected with Eimeria acervulina, E. maxima, or E. tenella were measured using a 10K cDNA microarray.  Based on a cutoff of > 2.0-fold differential expression compared with uninfected controls, relatively equal numbers of transcripts were altered by the three Eimeria infections at 1, 2, and 3 days post-primary infection.  By contrast, E. tenella elicited the greatest number of altered transcripts at 4, 5, and 6 days post-primary infection, and at all time points following secondary infection.  When analyzed on the basis of up- or down-regulated transcript levels over the entire 6 day infection periods, approximately equal numbers of up-regulated transcripts were detected following E. tenella primary (1,469) and secondary (1,459) infections, with a greater number of down-regulated mRNAs following secondary (1,063) vs. primary (890) infection.  On the contrary, relatively few mRNA were modulated following primary infection with E. acervulina (35 up, 160 down) or E. maxima (65 up, 148 down) compared with secondary infection (E. acervulina, 1,142 up, 1,289 down; E. maxima, 368 up, 1,349 down).  With all three coccidia, biological pathway analysis identified the altered transcripts as belonging to the categories of "Disease and Disorder" and "Physiological System Development and Function".  Sixteen intracellular signaling pathways were identified from the differentially expressed transcripts following Eimeria infection, with the greatest significance observed following E. acervulina infection.  Taken together, this new information will expand our understanding of host-pathogen interactions in avian coccidiosis and contribute to the development of novel disease control strategies.


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