IL-17A regulates Eimeria tenella schizont maturation and migration in avian coccidiosis

Authors: DEL CACHO, EMILIO - US Department Of Agriculture (USDA); GALLEGO, MARGARITA - University Of Zaragoza; Lillehoj, Hyun; QUILEZ, JOAQUIN - University Of Zaragoza; SANCHEZ-ACEDO, CARIDAD - University Of Zaragoza

Submitted to: Veterinary Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/12/2014
Publication Date: 2/26/2014
Publication URL: http://handle.nal.usda.gov/10113/61645
Citation: Del Cacho, E., Gallego, M., Lillehoj, H.S., Quilez, J., Sanchez-Acedo, C. 2014. IL-17A regulates Eimeria tenella schizont maturation and migration in avian coccidiosis. Veterinary Research Communications. 45:25.

Interpretive Summary: Avian coccidiosis is a serious intestinal infection which is caused by several distinct species of protozoan parasites, Eimeria. The ability to control this infection will reduce economic losses and mitigate the use of antibiotics in poultry production. In this report, ARS scientists and scientists at University of Zaragosa in Spain collaborated to investigate the role of one of the major immune effector molecules called interleukin 17 (IL-17). IL-17 is a recently described chicken protein which mediates inflammatory response. However their role in host response to avian coccidiosis is limited. Using a mouse-derived protien antibody which specifically detects chicken IL-17 which specifically detects and binds chicken IL-17 thereby blocking its biological activity, these scientists discovered that elimination of IL-17 activity in chickens significantly enhanced one type of immune cell Th1 and reduced the severity of infection. This is the first scientific evidence that demonstrates the role of chicken IL-17 in avian coccidiosis and this result provides a logical future strategy to mitigate the gut damages due to infection with intestinal parasites.

Technical Abstract: Although IL17A is associated with the immunological control of various infectious diseases, its role in host response to Eimeria infections is not well understood. In an effort to better dissect the role of IL17A in host-pathogen interactions in avian coccidiosis, a neutralizing antibody (Ab) to chicken IL17A was used in vivo to counteract IL17A bioactivity in vivo. Chickens infected with Eimeria tenella and treated intravenously with IL17A Ab, exhibited reduced intracellular schizont and merozoite development, and diminished oocyst formation, compared with untreated controls. Immunohistological evaluation of cecal lesions in the parasitized tissues indicated reduced migration and maturation of second-generation schizonts and reduced lesions. In contrast, untreated and infected chickens had epithelial cells harboring second-generation schizonts deep within the intestinal mucosa, maturing into second-generation merozoites. Furthermore, IL17A Ab treatment was associated with increased parameters of Th1 immunity, reduced levels of reactive oxygen species (ROS), and diminished levels of serum matrix metalloproteinase-9 (MMP-9). Finally, schizonts from untreated and infected chickens expressed S100, WASF3, and HSP70 proteins as merozoites matured, whereas the expression of these proteins was absent in IL17A Ab-treated chickens. These results provide the first evidence that the administration of an IL17A neutralizing Ab to E. tenella-infected chickens inhibits the migration of parasitized epithelial cells, markedly reduces the production of ROS and MMP-9, and decreases cecal lesions, suggesting that IL17A might be a potential therapeutic target for coccidiosis control.