SP-A MOUSE MODELS OF PNEUMOCYSTIS INFECTION

点击翻译按钮获取中文摘要

Pneumocystis carinii (Pc) is a fungus of low virulence that is major cause of pneumonia (P) in HIV patients. Surfactant protein (SP-A), a member of the collectins, plays an important role in the host's innate immunity against pulmonary pathogens. Studies of the interaction of SP-A with Pc have mainly been conducted in vitro and have produced conflicting results. Gene targeted mice deficient in SP-A appear more susceptible to PcP than wild type mice administered the same immunosuppression. The application proposes the following hypotheses: SP-A facilitates the clearance of Pc in the immunocompetent host; this activity can be localized to specific domains of SP-A and is mediated at least in part by alveolar macrophages; SP-A delays the development and reduces the severity of PcP in the immunocompromised host; SP-A down regulates the host immune/inflammatory response to Pc. The specific aims are: 1) To analyze the effects of SP-A on Pc infection in the immunocompetent host. These studies will: 1.1) investigate the effects of SP-A on the clearance of Pc from the lungs; 1.2) determine if the administration of SP-A can reverse the changes in SP-A deficient mice and to localize the specific domains involved; 1.3) study the effects of SP-A on the interaction of Pc with alveolar macrophages; and 1.4) analyze the effects of SP-A on the host immune/inflammatory response to Pc infection. 2) To analyze the effects of SP-A on PcP in the immunocompromised host. These studies will: 2.1) analyze the effects of SP-A on the development of PcP induced by different forms of immunosuppression; 2.2) examine the influence of SP-A on the changes in alveolar cells, sufactant constituents, and lung function that occur with PcP; and 2.3) analyze the influence of SP-A on the host immune/inflammatory response that occurs during the recovery from PcP.