Cytokine and goblet cell gene expression in equine cyathostomin infection and larvicidal anthelmintic therapy

Abstract

Aims:The role of the immune response to cyathostomin infections in horses remains unknown. Intestinal goblet cell hyperplasia has previously been noted as a component in cyathostomin infection; however, the function is unclear. The goal of this study was to evaluate the local and systemic gene expression to cyathostomin infections following larvicidal treatment and explore their relation to goblet cells. Methods and Results: Thirty-six ponies with naturally acquired cyathostomin infections were randomly allocated into three groups: fenbendazole-treated (10 mg/kg PO 5 days), moxidectin-treated (0.4 mg/kg PO once) and untreated control. Whole blood from all horses was collected weekly, and tissue samples from the large intestine collected during necropsy at 2 and 5 weeks post-treatment (WPT). Gene expression of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-22, IFN-γ, resistin-like molecule beta (RELM-β), Mucin 2 (MUC2) and tumour necrosis factor (TNF)-α was measured using qRT-PCR. There were statistically significant linear correlations between luminal worm burdens and MUC2 (r = −.2358) and RELM-β (r = −.2261). Conclusion: This suggests an active role of immune system post-treatment in parasite expulsion, specifically in goblet cells, and that the organs respond differently to treatment and the larvae themselves. This may have implications in the disease process and treatment. K E Y W O R D S anthelmintic, cyathostomin, equine, goblet cell, inflammation, larvicidal, worm expulsion S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Steuer AE, Stewart JC, Barker VD, Adams AA, Nielsen MK. Cytokine and goblet cell gene expression in equine cyathostomin infection and larvicidal anthelmintic therapy. Parasite Immunol. 2020;42:e12709.

Comparison of the host response to larvicidal and nonlarvicidal treatment of naturally acquired cyathostomin infections in horses

“…Previous studies have evaluated the inflammatory reaction to ivermectin and compared it to oxibendazole, moxidectin and a few other products 2,11,19 . These studies noted no differences between the treatment groups; however, intestinal erythema, oedema and ulceration following worm burdens were noted, 2,19,20 which is consistent with our previous findings 14,21 …”

“…2,11,19 These studies noted no differences between the treatment groups; however, intestinal erythema, oedema and ulceration following worm burdens were noted, 2,19,20 which is consistent with our previous findings. 14,21 Only one study, thus far, has evaluated cytokine gene expression in large intestinal tissues of horses with and without large intestinal disease, including three cases of larval cyathostominosis. 22 They found that tumour necrosis factor (TNF)-α was expressed in horses with inflammatory bowel disease; however, there were no significant differences between the groups with and without large intestinal disease.…”

Bugs and drugs: a systems biology approach to characterising the effect of moxidectin on the horse’s faecal microbiome

“…have previously been associated with inflammation in the gut and detected in humans and mice prior to the onset of colitis [24]. Recently Steurer et al [25] reported an interaction between larvicidal anthelmintic treatment, cyathostomin expulsion from the mucosa and MUC2 gene expression in goblet cells following moxidectin treatment. These data lead us to speculate that an increase in the relative abundance of Deferribacter spp.…”

Retrospective Evaluation of the Most Frequently Observed Histological Changes in Duodenal and Rectal Mucosal Biopsies in Horses with Recurrent Colic

“…According to the available knowledge, goblet cells are an integral part of the organ epithelial barrier and produce mucin products and play an important role in the immune response to mucosal antigens (e.g., parasites) [ 31 ]. The observed congestion of blood in the vessels may result from the formation of blood clots, which is a consequence of the release of inflammatory mediators from damaged epithelial and/or endothelial cells (activation of the antifibrinolytic coagulation cascade) [ 32 , 33 ].…”