Indole treatment alleviates intestinal tissue damage induced by chicken coccidiosis through activation of the aryl hydrocarbon receptor

Authors: KIM, WOO HYUN - US Department Of Agriculture (USDA); Lillehoj, Hyun; MIN, WONGI - Gyeongsang National University

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/4/2019
Publication Date: 3/26/2019
Citation: Kim, W., Lillehoj, H.S., Min, W. 2019. Indole treatment alleviates intestinal tissue damage induced by chicken coccidiosis through activation of the aryl hydrocarbon receptor. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2019.00560.
DOI: https://doi.org/10.3389/fimmu.2019.00560

Interpretive Summary: Coccidiosis which is caused by apicomplexan protozoan parasites of Eimeria spp. is one of the most economically important diseases affecting poultry production. After chickens ingest sporulated oocysts, sporozoites are released in the intestinal tract, invading intestinal epithelial cells for intracellular development. Invasion and egress of sporozoites and merozoites which are, two major invasive form of Eimeria lead to the destruction of the intestinal mucosa, thus resulting in local inflammation in the intestine. In this paper, ARS scientists showed that Indoles, which are phytochemicals that are very common in the body and diet and are abundant in Brassica (cruciferous) vegetables, including broccoli, brussels sprouts, cabbage, and cauliflower can regulate critical T lymphocytes involved in host response to coccidiosis and can ameliorate negative effects. There has been very limited information on the function of indole compounds in chickens and the roles of Treg and Th17 cells in chicken coccidiosis. The results of this paper identified the molecular pathways where indole can interfere with inflammatory response to reduce local damage in the intestine. This finding will be beneficial to scientist working on coccidiosis in their efforts to develop antibiotic alternatives to control coccidiosis.

Technical Abstract: Indoles, as the ligands of aryl hydrocarbon receptor (AhR), have been shown to possess immune-modulating property in terms of the balancing between regulatory T cells (Treg) and T helper 17 cells (Th17) activities. In the present study, we examined the effects of dietary indoles, 3,3’-diindolylmethane (DIM) and indole-3-carbinol (I3C)), on CD4+T cell population and functions in chickens. Furthermore, the effects of dietary DIM treatment on chicken coccidiosis infection model caused by an apicomplexan parasite were investigated. Dietary treatment of healthy chickens with DIM and I3C induced increased CD4+CD25+ (Treg) cells and the mRNA expression of IL-10, while decreasing number of CD4+IL-17A+ (Th17) cells and the mRNA levels of Th17-related cytokines, IL-17F, IL-21, and IL-22 in the intestine. In addition, we explored the role of AhR in indole-treated splenic lymphocytes by using AhR antagonist and our results suggested that DIM is a ligand for chicken AhR like in other mammals. In chicken coccidiosis, treatment of DIM increased ratio of Treg/Th17 cells and significantly reduced intestinal lesion in Eimeria tenella-infected cecum although no significant changes in body weight and fecal oocyst production were noted in DIM-treated chickens compared to non-treated control group. These results indicate that DIM is likely to affect the ratios of Treg/Th17 reducing the level of local inflammatory response induced by Eimeria or facilitate repairing process of inflamed gut following Eimeria infection. The results described herein are thus consistent with the concept that AhR ligand modulates the T cell immunity through the alteration of Treg/Th17 cells with Treg dominance. To our knowledge, present study is the first scientific report showing the effects of dietary indole on T cell immunity in poultry species.