SP-A MOUSE MODELS OF PNEUMOCYSTIS INFECTION

肺孢子虫感染的 SP-A 小鼠模型

• 批准号: 6735630
• 负责人: PETER D WALZER
• 金额: $ 38.25万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735630
• 关键词: Pneumocystis carinii; Pneumocystis pneumonia; alveolar macrophages; disease /disorder model; gene targeting; genetically modified animals; immunity; laboratory mouse; pulmonary surfactants

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.

卡氏肺孢子虫（Pc）是一种低毒力真菌， HIV感染者肺炎（P）。 表面活性剂蛋白（SP-A）， collectins，在宿主的天然免疫中起着重要的作用， 肺部病原体 关于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 SP-A缺陷小鼠似乎比野生型小鼠更容易受到PcP的影响 使用了相同的免疫抑制剂 申请书建议， 以下假设：SP-A促进Pc在 免疫活性宿主;这种活性可以定位于 SP-A至少部分由肺泡巨噬细胞介导; SP-A延迟了 发展和降低免疫功能低下的宿主中PcP的严重程度; SP-A下调宿主对Pc的免疫/炎症反应。 具体 目的：1）分析SP-A对Pc感染的影响， 免疫活性宿主。 这些研究将：1.1）调查 SP-A对Pc从肺中清除的影响; 1.2）确定 施用SP-A可以逆转SP-A缺陷小鼠的变化， 定位所涉及的特定结构域; 1.3）研究SP-A对 Pc与肺泡巨噬细胞的相互作用;以及1.4）分析 SP-A对宿主对Pc感染的免疫/炎症反应的影响。 2)分析 SP-A对免疫受损宿主中PcP的影响。 这些研究将： 2.1)分析SP-A对PcP形成的影响 不同形式的免疫抑制; 2.2）检查SP-A对 肺泡细胞、表面活性成分和肺功能的变化， 2.3）分析SP-A对宿主的影响 免疫/炎症反应发生在从PcP恢复期间。

项目成果

Sensitized splenocytes result in deleterious cytokine cascade and hyperinflammatory response in rats with Pneumocystis pneumonia despite the presence of corticosteroids.

尽管存在皮质类固醇，但敏化的脾细胞仍会导致肺孢子虫肺炎大鼠产生有害的细胞因子级联反应和高炎症反应。

• DOI: 10.1128/iai.72.2.757-765.2004
• 发表时间: 2004
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Thullen,TimothyD;Ashbaugh,AlanD;Daly,KieranR;Linke,MichaelJ;Steele,PaulE;Walzer,PeterD
• 通讯作者: Walzer,PeterD

Resolution of Pneumocystis murina infection following withdrawal of corticosteroid induced immunosuppression.

停用皮质类固醇诱导的免疫抑制后，鼠肺孢子虫感染得到缓解。

• DOI: 10.1016/j.micpath.2005.10.002
• 发表时间: 2006
• 期刊: Microbial pathogenesis
• 影响因子: 3.8
• 作者: Linke,Michael;Ashbaugh,Alan;Demland,Jeffery;Koch,Judith;Tanaka,Reiko;Walzer,Peter
• 通讯作者: Walzer,Peter

Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure.

环境暴露后，小鼠肺孢子虫在免疫活性表面活性蛋白 A 缺陷小鼠中定植。

• DOI: 10.1186/1465-9921-10-10
• 发表时间: 2009-02-19
• 期刊: Respiratory research
• 影响因子: 5.8
• 作者: Linke MJ;Ashbaugh AD;Demland JA;Walzer PD
• 通讯作者: Walzer PD

New rat model of Pneumocystis pneumonia induced by anti-CD4(+) T-lymphocyte antibodies.

抗CD4(+)T淋巴细胞抗体诱导肺孢子虫肺炎新大鼠模型。

• DOI: 10.1128/iai.71.11.6292-6297.2003
• 发表时间: 2003
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Thullen,TimothyD;Ashbaugh,AlanD;Daly,KieranR;Linke,MichaelJ;Steele,PaulE;Walzer,PeterD
• 通讯作者: Walzer,PeterD

Anti-human immunodeficiency virus drugs are ineffective against Pneumocystis carinii in vitro and in vivo.

抗人类免疫缺陷病毒药物在体外和体内对卡氏肺孢子虫均无效。

• DOI: 10.1086/323991
• 发表时间: 2001
• 期刊: The Journal of infectious diseases
• 作者: Walzer,PD;Ashbaugh,A;Collins,M;Cushion,MT
• 通讯作者: Cushion,MT