Project 171253

Bacterial infection of the lower respiratory tract is a common illness and is also a leading cause of death. It is estimated that 5.6 million cases of community acquired pneumonia are treated annually in North America, resulting in over one million hospitalizations. Bacterial pneumonia is the most common infectious complication of HIV infection. In addition, pneumonia acquired in the hospital is the most common infection in intensive care units, and is associated with high mortality. White blood cells seek out and kill bacteria that enter the lungs - this is the principal mechanism by which humans fight lung infections. In previous research, our group identified two proteins, called Group V and Group X secretory phospholipases A2, in white blood cells. These results were published in the Journal of Biological Chemistry, a highly respected, peer-reviewed scientific journal. The purpose of the experiments described in the current grant application is to determine how Group V and Group X secretory phospholipases A2 help humans fight lung infections. To complete these proposed studies, we have obtained mice that have been genetically manipulated such that they lack either Group V and/or Group X secretory phospholipase A2. By infecting normal mice and mice that lack one (or both) of these proteins with bacteria that commonly cause pneumonia in humans, and comparing how well each mouse fights the infection, we will be able to define the role played by Group V and Group X secretory phospholipases A2 in the lung infections. The new knowledge gained through these studies will increase our understanding of the basics mechanisms involved in the immune response to bacterial infection of the lung, and may lead to the development of novel therapeutic options for patients with bacterial lung infections.

using genetically modified mice to define the role of Group V and Group X secretory phospholipases A2 in the immune response to pulmonary bacterial infections