Host-pathogen interactions in Mycoplasma bovis pneumonia of cattle

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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.