Comparative Biomedical Sciences Department, University of Wisconsin-Madison, Madison, WI 53706.
Medical Microbiology & Immunology Department, University of Wisconsin-Madison, Madison, WI 53706.
Poult Sci. 2019 Sep 1;98(9):3471-3480. doi: 10.3382/ps/pez064.
Coccidiosis is a major gastrointestinal disease caused by several Eimeria species in floor raised chickens. Feeding an antibody to interleukin 10 (aIL-10) ameliorates the negative symptoms of coccidiosis in broilers, i.e., lack of weight gain, decreased feed conversion, and mortality. IL-10 signals by forming a ligand-receptor complex with IL-10 Receptor 1 (IL-10 R1) and IL-10 Receptor 2 (IL-10 R2). In this study, we hypothesize oral antibodies to the IL-10 receptors will neutralize the IL-10 signaling pathway equal to or better than aIL-10 to act as an oral anti-coccidiosis immunotherapy. A total of 5 sequential feed trials, set up as a 4 (diet antibody) × 2 (Eimeria challenge) factorial design, tested oral egg yolk antibodies to a total of 6 IL-10 R1 epitopes and 3 IL-10 R2 epitopes compared to a control antibody diet. A total of 10 pens of 5 chicks/pen/diet antibody/Eimeria challenge were housed for 21 d. On day 3 of age, chicks were either infected or not infected with a 10× dose of an Eimeria vaccine containing Eimeria acervulina, Eimeria tenella, and Eimeria maxima. Pen feed consumption and mean body weights were assessed weekly (d1, d7, d14, and d21); fecal oocyst shedding was assessed on day 10. Data were analyzed using a 2-way ANOVA. No significant interaction on chick weight was observed in chicks fed IL-10 R1 antibodies compared to chicks fed the control antibody was observed. In studies evaluating aIL-10 R2 oral antibodies, infected chicks fed aIL-10 R2: epitope 1 overcame the negative effects of Eimeria infection and had similar 21-d body weight to uninfected chicks (P4 = 0.07). We hypothesized that feeding oral antibodies to the IL-10 receptors would result in equivalent anti-coccidial benefits to aIL-10. However, none of the 6 antibodies to IL-10 R1 epitopes yielded any benefits during Eimeria infection compared to controls. A total of 2 oral antibodies to IL-10 R2 showed promising results equivalent to the aIL-10 immunotherapeutic. Immunofluorescence staining shows that the IL-10R2 significantly increases in abundance in response to Eimeria infection, whereas IL-10R1 does not.
球虫病是由几种艾美耳球虫在离地饲养的鸡中引起的一种主要的胃肠道疾病。给鸡喂食白细胞介素 10（IL-10）抗体可以改善肉鸡的球虫病的负面症状，如体重增加缓慢、饲料转化率降低和死亡率升高。IL-10 通过与白细胞介素 10 受体 1（IL-10 R1）和白细胞介素 10 受体 2（IL-10 R2）形成配体-受体复合物来发出信号。在这项研究中，我们假设口服抗 IL-10 受体抗体将与 aIL-10 一样或更好地中和 IL-10 信号通路，作为一种口服抗球虫免疫疗法。总共进行了 5 次连续的饲料试验，采用 4（饮食抗体）×2（艾美耳球虫挑战）的析因设计，比较了口服蛋黄抗体对 6 个 IL-10 R1 表位和 3 个 IL-10 R2 表位，与对照抗体饮食相比。每组 10 个笼子，每个笼子 5 只小鸡/笼/饮食抗体/艾美耳球虫挑战，饲养 21 天。在 3 天大时，鸡要么感染要么不感染含有艾美耳球虫、柔嫩艾美耳球虫和巨型艾美耳球虫的 10×剂量疫苗。每周评估一次每只鸡的饲料消耗量和平均体重（第 1、7、14 和 21 天）；第 10 天评估粪便卵囊脱落。使用双因素方差分析对数据进行分析。与对照组相比，在喂食 IL-10 R1 抗体的小鸡中，没有观察到小鸡体重有显著的相互作用。在评估 aIL-10 R2 口服抗体的研究中，感染的鸡喂食 aIL-10 R2：表位 1 克服了艾美耳球虫感染的负面影响，21 天体重与未感染的鸡相似（P4 = 0.07）。我们假设口服抗 IL-10 受体抗体将产生与 aIL-10 相当的抗球虫效果。然而，与对照组相比，在艾美耳球虫感染期间，6 种针对 IL-10 R1 表位的抗体都没有产生任何益处。共有 2 种针对 IL-10 R2 的口服抗体显示出与 aIL-10 免疫治疗相当的有希望的结果。免疫荧光染色显示，IL-10R2 在艾美耳球虫感染后丰度显著增加，而 IL-10R1 则没有。
