Viral-bacterial co-infections of the differentiated airway epithelium by pathogens associated with the bovine respiratory disease complex

呼吸道共感染在现代集约化农业动物生产系统中起着重要作用。控制合并感染是一项具有挑战性的任务，因为与单一感染相比，发病机制要复杂得多。虽然这已经知道了很多年，但对病原体和宿主在共同感染中相互作用的分子机制知之甚少。在动物感染中研究这一点非常困难，因此，重要的是开发尽可能接近地模拟体内情况的合适的体外模型。本研究将分析牛呼吸道重要病原体对呼吸道上皮细胞的共感染。分析的病原体包括两种病毒和三种细菌，它们都被认为是 涉及牛呼吸道疾病复合体：牛呼吸道合酶病毒（BRSV）、牛副流感病毒3型（BPIV 3）、多杀性巴氏杆菌、溶血性曼氏杆菌和牛支原体。本项目是基于初步工作，其中我们分析了分化的气道上皮细胞的病毒单感染。使用两种用于分化的呼吸道上皮细胞的培养系统，精确切割的肺切片和气-液界面培养物，我们发现BPIV 3对气道细胞的感染是非常有效的，并且对上皮具有不利影响。相比之下，呼吸道上皮细胞对BRSV感染具有很大的抵抗力。该项目的目的是首先分析已经在M.牛这是其次是调查的共同感染。将解决以下问题：（i）BPIV 3感染的有害影响是否有利于随后被三种细菌因子之一感染？(ii)细菌感染是否使气道细胞对随后的BRSV感染易感？预期的结果将增加我们对S。说明重要的呼吸道病原体如何在牛肺中相互作用以诱发牛呼吸道疾病综合征的特征性症状。

Co-infections in the respiratory tract play an important role in modern intensive production systems of agricultural animals. Control of co-infections is a challenging task, since pathogenesis is much more complex as compared to mono-infections. Though this has been known for many years, little is known about the molecular mechanisms of interactions between pathogens and the host in co-Infections. It is very difficult to study this in animal infections and, therefore, it is important to develop suitable in vitro models which mimic the in vivo situation as closely as possible. In the proposed project, we will analyze the co-infection of airway epithelial cells by important pathogens of the bovine respiratory tract. The pathogens analyzed comprise two viruses and three bacteria that are all considered to be involved the bovine respiratory disease complex: bovine respiratory synzytial virus (BRSV), bovine parainfluenzavirus 3 (BPIV3), Pasteruella multocida, Mannheimia haemolytica und Mycoplasma bovis. This project is based on preliminary work in which we analyzed the viral mono-infection of differentiated airway epithelial cells. Using two cultural systems for differentiated respiratory epithelial cells, precision-cut lung slices and air-liquid-interface cultures, we found that infection of airway cells by BPIV3 is very efficient and has a detrimental effect on the epithelium. By contrast, cells of the respiratory epithelium turned out to be largely resistant against an infection by BRSV. Aim of the proposed project is first to analyze the bacterial mono-infection which has already been started in the case of M. bovis. This is followed by an inverstigation of the co-infection. The following will be addressed: (i) Does the detrimental effect of the BPIV3 infection favor a subsequent infection by one of the three bacterial agents? (ii) Does the bacterial infection render the airway cells susceptible for a subsequent infection by BRSV? The expected results will increase our understanding how S. suis how important respiratory pathogens interact in the bovine lung to induce the symptoms characteristic for the bovine respiratory disease complex.