A bovine model of respiratory Chlamydia psittaci infection: challenge dose titration.
A bovine model of respiratory Chlamydia psittaci infection: challenge dose titration.
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DOI：
10.1371/journal.pone.0030125
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sachse K
中科院分区：
文献类型：
--
作者：
Reinhold P;Ostermann C;Liebler-Tenorio E;Berndt A;Vogel A;Lambertz J;Rothe M;Rüttger A;Schubert E;Sachse K
本研究旨在建立和评价实验诱导的鹦鹉热肠弯曲菌急性感染的牛呼吸道模型。小牛是自然宿主，发病机制可能类似于人类的情况。将鹦鹉热菌DC15株经支气管镜以106~109个包涵体形成单位(IFU)四种不同攻毒剂量经支气管镜接种于2~3月龄犊牛。对照组接受紫外线灭活鹦鹉热杆菌或细胞培养液。106ifu/小牛只引起轻微的呼吸道感染，而107和108剂量则引起发热、呼吸急促、干咳和心动过速，接种后2-3天(Dpi)明显，持续约一周。在接触109ifu鹦鹉热菌的小牛中，呼吸系统疾病伴随着严重的全身疾病(冷漠、震颤、食欲显著下降)。在临床症状最明显的时间点(3dpi)，接种106和107ifu的犊牛肺部病变范围在肺组织的10%以下，接种108和109ifu鹦鹉热菌的犊牛约占15%，而接种109ifu鹦鹉热菌的犊则超过30%。除了临床症状和病理损害外，肺组织的细菌载量和肺部炎症标志物(即细胞计数、支气管肺泡灌洗液中蛋白质和二十烷基类物质的浓度)与鹦鹉热杆菌存活的IFU呈正相关。虽然内毒素的任何影响都已被排除，但所有的影响都可能归因于复制细菌的感染。综上所述，小牛代表了呼吸道衣原体感染的合适模型。剂量滴定显示，无论是临床潜伏感染还是临床显性感染，都可以通过106或108 ifu/c15鹦鹉弧菌进行实验复制，而超过108 ifu C.鹦鹉吸虫的剂量出于伦理原因不能推荐用于进一步研究。这个定义的衣原体感染不同临床表现的模型允许研究宿主和病原体的相互作用。
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 106 to 109 inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 106 ifu/calf resulted in a mild respiratory infection only, the doses of 107 and 108 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 109 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 106 and 107 ifu, about 15% in calves inoculated with 108 and more than 30% in calves inoculated with 109 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 106 or 108 ifu/calf of C. psittaci DC15 while doses above 108 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.
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3.3
作者：
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