Institute of Molecular Pathogenesis at 'Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany.
PLoS One. 2012;7(1):e30125. doi: 10.1371/journal.pone.0030125. Epub 2012 Jan 27.
This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2-3 months via bronchoscope at four different challenge doses from 10(6) to 10(9) inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 10(6) ifu/calf resulted in a mild respiratory infection only, the doses of 10(7) and 10(8) induced fever, tachypnea, dry cough, and tachycardia that became apparent 2-3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 10(9) ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 10(6) and 10(7) ifu, about 15% in calves inoculated with 10(8) and more than 30% in calves inoculated with 10(9) ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 10(6) or 10(8) ifu/calf of C. psittaci DC15 while doses above 10(8) ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions.
本研究旨在建立和评估一种牛呼吸道模型,用于实验诱导急性鹦鹉热衣原体感染。牛是天然宿主,发病机制可能类似于人类的情况。通过支气管镜对 2-3 月龄的犊牛进行支气管内接种,接种剂量分别为每只动物 10(6)至 10(9)个包涵体形成单位(ifu)的 C. psittaci 菌株 DC15 四种不同挑战剂量。对照组接受紫外线灭活的 C. psittaci 或细胞培养液。当每只犊牛接种 10(6)ifu 时,仅导致轻度呼吸道感染,而当剂量为 10(7)和 10(8)ifu 时,会引起发热、呼吸急促、干咳和心动过速,这些症状在接种后 2-3 天(dpi)出现,并持续约一周。在接种 10(9)ifu 的 C. psittaci 的犊牛中,呼吸道疾病伴有严重的全身疾病(冷漠、震颤、食欲明显减退)。在临床症状最明显的时间点(3dpi),接种 10(6)和 10(7)ifu 的犊牛肺部病变程度低于肺部组织的 10%,接种 10(8)ifu 的犊牛约为 15%,接种 10(9)ifu 的犊牛超过 30%。除临床症状和病理病变外,肺部组织的细菌负荷和肺部炎症标志物(即支气管肺泡灌洗液中的细胞计数、蛋白质和类二十烷酸浓度)与活 C. psittaci 的 ifu 呈正相关。虽然已排除内毒素的任何影响,但所有影响均可归因于复制细菌的感染。总之,犊牛是一种适合的呼吸道衣原体感染模型。剂量滴定表明,无论是 10(6)还是 10(8)ifu/只的 C. psittaci DC15,都可以在实验中复制临床潜伏期和临床显性感染,而由于伦理原因,不建议使用超过 10(8)ifu 的 C. psittaci 剂量进行进一步研究。这种不同临床表达的衣原体感染的模型定义允许研究宿主-病原体相互作用。