Animal infection models to study Mycobacterium avium subsp. paratuberculosis (MAP) infection are useful for evaluating the efficacy of vaccines and other therapeutics for the prevention or treatment of infection. The goal of the present study was to compare smaller ruminants, sheep and goats, with calves as infection models. Neonatal sheep, goats, and calves (n = 4) received 109 cfu of a cattle isolate of MAP in milk replacer on days 0, 3 and 6 in a 12-month study and sampled monthly thereafter. Results demonstrated a robust antigen-specific IFN-γ response at 90 days post-inoculation for sheep and goats, with lower responses noted for calves. By 360 days, IFN-γ responses were 50 and 82% higher for calves than for goats and sheep, respectively. Although MAP-specific antibody responses were first observed in sheep at 90 days, calves had higher antibody responses throughout the remainder of the study. Following pass-through shedding on day 7, fecal shedding was fairly negligible across treatments but remained higher for calves throughout the study. Colonization of tissues was variable within treatment group and was higher for calves and sheep for the majority of tissues. Upon antigen stimulation of PBMCs, higher populations of CD4 + T cells cells and lower populations of γδ TCR + and NK cells were observed for goats and calves compared to sheep. Relative gene expression of IL-4, IL-12, and IL-17 in PBMCs was higher in goats, corresponding to lower tissue colonization with MAP. These data suggest that ruminant species are fairly comparable as infection models for MAP, but discrete differences in host responses to MAP infection exist between species.

中文翻译：

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绵羊，山羊和犊牛作为鸟分枝杆菌亚种感染模型的比较。副结核病。

用于研究鸟分枝杆菌亚种的动物感染模型。副结核病（MAP）感染可用于评估疫苗或其他疗法预防或治疗感染的功效。本研究的目的是比较较小的反刍动物，绵羊和山羊，以犊牛为感染模型。在一项为期12个月的研究中，第0、3和6天，新生绵羊，山羊和犊牛（n = 4）在代乳品中接受了109 cfu的MAP牛分离株，此后每月进行采样。结果表明，绵羊和山羊接种后90天有很强的抗原特异性IFN-γ反应，而犊牛的反应则较低。到360天时，犊牛的IFN-γ反应分别比山羊和绵羊高50％和82％。尽管在90天时首次在绵羊中观察到MAP特异性抗体反应，在整个研究的其余时间内，小牛的抗体反应较高。在第7天通过脱落后，粪便脱落在所有处理中均可以忽略不计，但在整个研究过程中，犊牛的粪便脱落仍然较高。在治疗组中，组织的定植是可变的，对于小牛和绵羊，大多数组织的定植更高。在对PBMCs进行抗原刺激后，与绵羊相比，山羊和牛犊的CD4 + T细胞细胞数量较高，而γδTCR +和NK细胞数量较低。山羊PBMCs中IL-4，IL-12和IL-17的相对基因表达较高，这对应于MAP引起的较低的组织定植。这些数据表明，反刍动物物种与MAP的感染模型相当，但是物种之间存在宿主对MAP感染反应的离散差异。