Animal Parasitic Diseases Lab, USDA/ARS, Beltsville, MD 20705, USA.
Animal Parasitic Diseases Lab, USDA/ARS, Beltsville, MD 20705, USA.
Vet Parasitol. 2021 Aug;296:109510. doi: 10.1016/j.vetpar.2021.109510. Epub 2021 Jun 26.
Bovine ostertagiasis causes significant production losses to the cattle industry. Protective immunity induced by natural infection is slow to develop and anthelmintic resistance is rapidly developing. There is a need to advance alternatives for control of gastrointestinal nematode parasites. The present study investigated the effects of repeated, drug-truncated infections (rDTI) on development of protective immunity and attenuation of a challenge infection by O. ostertagi. Helminth-free calves were randomly assigned to either a rDTI or a control group (n = 5). The rDTI group received daily oral infections of 5000 Ostertagia L3 for 5 consecutive days, then were drug-treated on 14 and 15 days post infection (dpi), to attenuate O. ostertagi at the late fourth larval (L4) through young adult stages. DTI was repeated 3 weeks after the drug treatment. A total of 5 DTIs were administered to the DTI-treated animals. Non-DTI-treated, control animals received tap water as infection control. All animals were drug-treated at the same time. Animals were challenge-infected 4 weeks following the final round of rDTI. The results show that eggs per gram of feces (EPG) in the rDTI group were significantly reduced (P < 0.05) from 21 to 39 dpi, with an overall reduction in cumulative EPG. The control group exhibited reduced (P = 0.0564) average weight gains when compared to those of the rDTI group during weeks 4-5 post infection, a period coinciding with peak EPG output of control animals. Antigen-specific IgG, IgE and IgA responses were detected after the 2nd DTI, and stronger antibody recall responses were elicited by challenge infection. High levels of antigen-specific peripheral blood mononuclear cell (PBMC)/T cell proliferation to whole worm and excretory-secretory (ES) antigens were detected in rDTI-treated animals. These data indicate that partial protective immunity against ostertagiasis, involving cell-mediated and humoral responses, can be attained by rDTI which allowed for maximal antigen exposure from staggered parasitic developmental stages. The data suggest that rDTI can be used as a model to study host-parasite interactions and identify parasite antigens responsible for eliciting host protective immune responses.
牛奥斯特拉线虫病给养牛业造成了重大的生产损失。自然感染诱导的保护性免疫发展缓慢，驱虫药耐药性迅速发展。因此，需要开发替代方法来控制胃肠道线虫寄生虫。本研究调查了重复药物截断感染（rDTI）对奥斯特拉线虫保护性免疫的发展和挑战感染的减弱的影响。无蠕虫小牛被随机分配到 rDTI 组或对照组（n = 5）。rDTI 组连续 5 天每天口服感染 5000 个奥斯特拉线虫 L3，然后在感染后第 14 和 15 天进行药物治疗，以在第四期幼虫（L4）晚期至幼成虫阶段减弱奥斯特拉线虫。药物治疗后 3 周重复 DTI。总共给 DTI 处理的动物进行了 5 次 DTI。未接受 DTI 治疗的对照组动物接受自来水作为感染对照。所有动物同时接受药物治疗。在最后一轮 rDTI 后 4 周对动物进行了挑战感染。结果表明，rDTI 组的粪便每克卵数（EPG）从 21 天到 39 天显著减少（P <0.05），累积 EPG 总体减少。与 rDTI 组相比，对照组在感染后第 4-5 周的平均体重增加减少（P = 0.0564），这一时期与对照动物 EPG 输出的高峰期相吻合。在第二次 DTI 后检测到抗原特异性 IgG、IgE 和 IgA 反应，并且通过挑战感染引发了更强的抗体回忆反应。在 rDTI 处理的动物中检测到针对全虫和排泄分泌（ES）抗原的高水平的抗原特异性外周血单核细胞（PBMC）/T 细胞增殖。这些数据表明，通过 rDTI 可以获得针对奥斯特拉线虫病的部分保护性免疫，涉及细胞介导和体液反应，从而允许从交错的寄生虫发育阶段获得最大的抗原暴露。数据表明，rDTI 可作为研究宿主-寄生虫相互作用和鉴定引起宿主保护性免疫反应的寄生虫抗原的模型。
