Host-pathogen interactions in Mycoplasma bovis pneumonia of cattle

牛支原体已成为引起牛细菌性肺炎的主要原因。它对加拿大牛肉和乳制品行业具有经济重要性，是一个福利问题，因为动物患有慢性疾病，呼吸道疾病是牛肉生产中预防性使用抗生素的主要原因。然而，由于缺乏对这种突发疾病如何发展的了解，控制方法受到限制。此外，M.牛肺炎是最重要的，因为许多临床上正常的小牛都有M。牛的细菌在他们的肺部，感染的结果基本上取决于宿主因素，和其他细菌几乎总是存在。因此，这种自然疾病是多微生物肺病的模型，其中随着疾病的发展和进展，肺部被可预测的细菌序列感染。这些研究调查了这些细菌和宿主细胞之间的相互作用如何决定感染是否受到控制和静止，或者诱导组织损伤和炎症。** 首先，我们确定了M.牛会引起肺损伤。假设M.牛不直接损伤肺组织，而是激活肺泡巨噬细胞分泌损害肺的产物。为了研究，将巨噬细胞感染M。我们将测量脂肪酶和蛋白酶的产生，以及它们对损伤肺细胞和降解对肺功能重要的表面活性剂磷脂和蛋白质的影响。** 第二，我们确定病变肺的微环境如何影响巨噬细胞对M.牛传染病假设是先前的细胞死亡或炎症导致巨噬细胞对M.牛感染，以促进炎症和组织损伤的方式，而不是容忍和控制感染。在用M感染巨噬细胞之前，巨噬细胞将在体外暴露于炎症介质、细菌产物或死细胞。牛，并测量对细菌杀灭、炎症和肺损伤的作用。同样的假设将在体内进行研究，重点是并发感染、肺损伤或炎症如何影响M。牛的感染总之，这些研究解决了宿主-病原体相互作用的基本方面，包括组织微环境（坏死和炎症）的预先存在的异常如何影响宿主对细菌感染的反应，从而影响所产生疾病的性质。此外，这些研究提供了关于牛支原体肺炎如何发展的关键信息，以及为什么一些受感染的小牛会患病，而另一些则保持健康。这方面的知识，预计将直接为加拿大牛肉和奶制品行业带来实际利益，导致改善控制这一重要疾病的方法。

Mycoplasma bovis has emerged as a major cause of bacterial pneumonia in cattle. It is of economic importance to the Canadian beef and dairy industries, is a welfare issue because of animal suffering from chronic disease, and respiratory disease is a major reason for preventative use of antibiotics in beef production. However, control methods are limited by a lack of understanding of how this emergent disease develops. Furthermore, M. bovis pneumonia is of fundamental interest because many clinically normal calves have M. bovis bacteria in their lungs, the outcome of infection depends substantially on host factors, and other bacteria are nearly always present. Thus, this natural disease is a model of polymicrobial lung disease, in which the lung is infected by a predictable sequence of bacteria as disease develops and progresses. These studies investigate how interactions among these bacteria and host cells determine whether infection is controlled and quiescent or alternatively induces tissue damage and inflammation. ******First, we determine the specific ways by which M. bovis incites damage to the lung. The hypothesis is that M. bovis does not directly injure lung tissue, but instead activates pulmonary alveolar macrophages to secrete products that damage the lung. To investigate, macrophages will be infected with M. bovis, and we will measure production of lipases and proteases as well as their effect on damaging lung cells and degrading the surfactant phospholipids and proteins that are important for lung function. ******Second, we determine how the microenvironment of the diseased lung influences how macrophages respond to M. bovis infection. The hypothesis is that prior cell death or inflammation causes macrophages respond to M. bovis infection in a way that promotes inflammation and tissue damage instead of tolerating and controlling the infection. Macrophages will be exposed in vitro to inflammatory mediators, bacterial products, or dead cells prior to infecting the macrophages with M. bovis, and the effects on bacterial killing, inflammation and lung damage are measured. The same hypothesis will be investigated in vivo, focusing on how concurrent infection, lung damage or inflammation influence the outcome of M. bovis infection.******Together, these studies address fundamental aspects of host-pathogen interaction including how pre-existing abnormalities of the tissue microenvironment (necrosis and inflammation) influence the host response to bacterial infection and thus the nature of the resulting disease. Further, these studies provide key information on how Mycoplasma bovis pneumonia develops, and why some infected calves develop disease while others remain healthy. This knowledge is expected to be of direct practical benefit for the Canadian beef and dairy industries by leading to methods for improved control of this important disease.