Chilvers E R, Spreadbury C L, Cohen J
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Mycopathologia. 1989 Dec;108(3):163-71. doi: 10.1007/BF00436221.
A rabbit model of invasive aspergillosis has been used to investigate the pathogenesis of Aspergillus infection in the immunosuppressed host. The animals received hydrocortisone daily and a single dose of cyclophosphamide 2 days prior to intratracheal instillation of conidia from Aspergillus fumigatus. Bronchoalveolar lavage (BAL) was performed in 3 infected and 2 control saline treated animals sacrificed on days 1, 2, 4, 7 and 10 following inoculation. Infective load within the lung was quantified using an assay for chitin which is an important component of fungal cell walls (in particular the hyphal cell wall) and is not present in vertebrate tissue. The total BAL white cell count did not discriminate between infected and saline treated animals and Aspergillus was cultured from one lavage specimen only. Infected animals developed a marked neutrophil alveolitis by day 2 in contrast to a near total absence of neutrophils in the lavages of the control animals. Phagocytosis of conidia by alveolar macrophages was prominent but did not prevent progressive infection as confirmed by measurement of lung chitin. This pattern of cellular response within the alveolar airspace reflects the complex nature of the response to Aspergillus infection in the immunosuppressed host.
侵袭性曲霉病的兔模型已被用于研究免疫抑制宿主中曲霉菌感染的发病机制。动物每天接受氢化可的松治疗，并在经气管内滴注烟曲霉菌分生孢子前2天接受单次剂量的环磷酰胺治疗。在接种后第1、2、4、7和10天，对3只感染动物和2只接受生理盐水治疗的对照动物实施支气管肺泡灌洗（BAL）。使用针对几丁质的检测方法对肺内的感染负荷进行定量，几丁质是真菌细胞壁（特别是菌丝细胞壁）的重要组成部分，不存在于脊椎动物组织中。支气管肺泡灌洗的白细胞总数无法区分感染动物和接受生理盐水治疗的动物，仅从一个灌洗样本中培养出曲霉菌。与对照动物灌洗中几乎完全没有中性粒细胞形成对比的是，感染动物在第2天出现了明显的中性粒细胞肺泡炎。肺泡巨噬细胞对分生孢子的吞噬作用很显著，但正如通过测量肺几丁质所证实的那样，这并不能阻止感染的进展。肺泡腔隙内的这种细胞反应模式反映了免疫抑制宿主对曲霉菌感染反应的复杂性。
