SP-A MOUSE MODELS OF PNEUMOCYSTIS INFECTION

卡氏肺囊虫 (Pc) 是一种低毒力真菌，是引起 HIV 患者肺炎 (P)。 表面活性蛋白（SP-A），是 集合素，在宿主的先天免疫中发挥重要作用 肺部病原体。 SP-A与Pc相互作用的研究主要有 在体外进行并产生了相互矛盾的结果。 基因靶向 缺乏 SP-A 的小鼠似乎比野生型小鼠更容易受到 PcP 的影响 给予相同的免疫抑制。 该申请提出 以下假设：SP-A 促进 Pc 的清除 免疫能力强的宿主；这项活动可以局限于特定领域 SP-A 至少部分由肺泡巨噬细胞介导； SP-A 延迟 免疫功能低下宿主中 PcP 的发生并降低其严重程度； SP-A 下调宿主对 PC 的免疫/炎症反应。 具体的 目的是： 1) 分析 SP-A 对 PC 感染的影响 具有免疫能力的宿主。 这些研究将： 1.1）调查以下因素的影响： SP-A 对肺中 Pc 清除率的影响； 1.2) 确定是否 给予 SP-A 可以逆转 SP-A 缺陷小鼠的变化，并 本地化所涉及的特定领域； 1.3）研究SP-A对 Pc与肺泡巨噬细胞的相互作用； 1.4）分析影响 SP-A 对 PC 感染的宿主免疫/炎症反应的影响。 2）分析 SP-A 对免疫功能低下宿主 PcP 的影响。 这些研究将： 2.1）分析SP-A对PcP诱导的发展的影响 不同形式的免疫抑制； 2.2)考察SP-A对 肺泡细胞、表面活性剂成分和肺功能的变化 与 PcP 一起发生； 2.3）分析SP-A对宿主的影响 PcP 恢复期间发生的免疫/炎症反应。

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.