Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia.
Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia.
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DOI：
10.1371/journal.pone.0188251
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Gruber AD
中科院分区：
文献类型：
--
作者：
Dietert K;Gutbier B;Wienhold SM;Reppe K;Jiang X;Yao L;Chaput C;Naujoks J;Brack M;Kupke A;Peteranderl C;Becker S;von Lachner C;Baal N;Slevogt H;Hocke AC;Witzenrath M;Opitz B;Herold S;Hackstein H;Sander LE;Suttorp N;Gruber AD
肺炎可能由多种病原体引起，被认为是人类最常见的传染性死亡原因。小鼠急性肺部感染模型在许多方面反映了人类病理，有助于我们对该疾病的理解和新治疗策略的开发。尽管组织成像的其他领域取得了进展，但组织病理学仍然是对小鼠肺炎和治疗干预进行描述性和半定量评估的最具决定性和实用性的读出工具。在这里，我们系统地描述和比较了由肺炎链球菌（S.）、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、嗜肺军团菌、大肠杆菌、中东呼吸综合征（MERS）冠状病毒、甲型流感病毒（IAV）和IAV引起的肺炎与肺炎链球菌重叠感染引起的小鼠急性肺炎模型的独特组织病理学特征。模型的系统比较揭示了病变分布、肺炎诱发特征、主要炎症细胞类型、邻近组织病变以及组织切片中病原体检出率的显着差异。因此，我们为每个模型确定了适合实际半定量评分系统的核心标准，该系统考虑了肺炎的病原体和模型特异性模式。讨论了影响实验病理学的其他关键因素，包括感染剂量、时间动力学和小鼠品系的遗传背景。模型特异性病理学之间的巨大差异强调了针对实验结果进行比较量化的病原体和模型适应标准的必要性。这些标准还允许对临床前模型中的治疗策略进行标准化验证和比较。
Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. pneumoniae. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models.
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影响因子：
15.9
作者：
Al-Tawfiq JA;Memish ZA
通讯作者：
Memish ZA
影响因子：
5.8
作者：
Hackstein H;Lippitsch A;Krug P;Schevtschenko I;Kranz S;Hecker M;Dietert K;Gruber AD;Bein G;Brendel C;Baal N
通讯作者：
Baal N
影响因子：
1.8
作者：
Gillet, Y;Issartel, B;Floret, D
通讯作者：
Floret, D
影响因子：
5.5
作者：
Alharbi NK;Padron-Regalado E;Thompson CP;Kupke A;Wells D;Sloan MA;Grehan K;Temperton N;Lambe T;Warimwe G;Becker S;Hill AVS;Gilbert SC
通讯作者：
Gilbert SC
影响因子：
3.4
作者：
Archer KA;Alexopoulou L;Flavell RA;Roy CR
通讯作者：
Roy CR