Köhler Heike, Soschinka Anneka, Meyer Michaela, Kather Angela, Reinhold Petra, Liebler-Tenorio Elisabeth
Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany.
Present address: Tierärztliche GmbH Hagenow, Hagenow, Germany.
BMC Vet Res. 2015 Mar 24;11:74. doi: 10.1186/s12917-015-0381-1.
Paratuberculosis caused by Mycobacterium avium subsp. paratuberculosis (MAP) is difficult to control due to a long phase of clinically non-apparent (latent) infection for which sensitive diagnostics are lacking. A defined animal model for this phase of the infection can help to investigate host-MAP interactions in apparently healthy animals and identify surrogate markers for disease progress and might also serve as challenge model for vaccines. To establish such a model in goats, different age at inoculation and doses of oral inoculum of MAP were compared. Clinical signs, faecal shedding as well as MAP-specific antibody, IFN-γ and IL-10 responses were used for in vivo monitoring. At necropsy, about one year after inoculation (pi), pathomorphological findings and bacterial organ burden (BOB) were scored.
MAP infection manifested in 26/27 inoculated animals irrespective of age at inoculation and dose. Clinical signs developed in three goats. Faecal shedding, IFN-γ and antibody responses emerged 6, 10-14 and 14 wpi, respectively, and continued with large inter-individual variation. One year pi, lesions were detected in 26 and MAP was cultured from tissues of 23 goats. Positive animals subdivided in those with high and low overall BOB. Intestinal findings resembled paucibacillary lesions in 23 and multibacillary in 4 goats. Caseous and calcified granulomas predominated in intestinal LNN. BOB and lesion score corresponded well in intestinal mucosa and oGALT but not in intestinal LNN.
A defined experimental infection model for the clinically non-apparent phase of paratuberculosis was established in goats as suitable basis for future studies.
由副结核分枝杆菌(MAP)引起的副结核病难以控制,因为其存在较长的临床无明显症状(潜伏)感染阶段,且缺乏敏感的诊断方法。针对该感染阶段建立明确的动物模型有助于研究表面健康动物体内宿主与MAP的相互作用,识别疾病进展的替代标志物,还可作为疫苗的攻毒模型。为在山羊中建立这样的模型,比较了不同接种年龄和MAP口服接种剂量。利用临床症状、粪便排菌情况以及MAP特异性抗体、IFN-γ和IL-10反应进行体内监测。在接种后约一年进行尸检时,对病理形态学发现和细菌器官负荷(BOB)进行评分。
27只接种动物中有26只出现MAP感染,与接种年龄和剂量无关。三只山羊出现临床症状。粪便排菌、IFN-γ和抗体反应分别在接种后6周、10 - 14周和14周出现,并在个体间存在较大差异的情况下持续存在。接种后一年,在26只山羊中检测到病变,23只山羊的组织培养出MAP。阳性动物分为总体BOB高和低的两组。23只山羊的肠道病变类似少菌型病变,4只山羊类似多菌型病变。干酪样和钙化肉芽肿在肠道局部淋巴结中占主导。肠道黏膜和oGALT中的BOB与病变评分相关性良好,但在肠道局部淋巴结中并非如此。
在山羊中建立了副结核病临床无明显症状阶段明确的实验感染模型,为未来研究提供了合适的基础。