Immune Responses During Pneumocystis Carinii Pneumonia

卡氏肺孢子虫肺炎期间的免疫反应

• 批准号: 7212392
• 负责人: JOSEPH A KOVACS
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7212392
• 关键词: HIV infections; Pneumocystis carinii; Pneumocystis pneumonia; SCID mouse; cytokine; disease /disorder model; gene expression; host organism interaction; hypoxia; immune response; immunodeficiency; immunoregulation; inflammation; laboratory mouse; microarray technology; microorganism genetics; microorganism immunology; polymerase chain reaction

Pneumocystis is a major pathogen of patients with HIV infection. The immune responses to Pneumocystis are poorly understood, but cytokines may play a role in both clearing Pneumocystis infection and in the hypoxia associated with Pneumocystis pneumonia that may be exacerbated following initiation of therapy. We are using the scid mouse model, as well as other immunodeficient mice, to further evaluate the role of individual cytokines and other immunoregulatory molecules in modulating Pneumocystis infection. We have developed a real time PCR assay to quantitate Pneumocystis over a wide dynamic range, and are currently examining Pneumocystis infection in healthy animals to better understand immune responses in the normal host. Using microarrays, we have been able to identify genes that are differentially expressed during Pneumocystis infection in healthy compared to immunodeficient mice; the majority of differentially expressed genes are related to the immune system. It is hoped that these studies will provide insights into the mechanisms critical for control of Pneumocystis infection in the healthy host, and may provide mechanisms for increasing clearance of Pneumocystis or decreasing the inflammation that may be causing hypoxia.

肺孢子菌是HIV感染者的主要病原体。对肺孢子虫的免疫反应知之甚少，但细胞因子可能在清除肺孢子虫感染和与肺孢子虫肺炎相关的缺氧中发挥作用，而肺孢子虫肺炎在治疗开始后可能会加剧。我们正在使用 scid 小鼠模型以及其他免疫缺陷小鼠来进一步评估个体细胞因子和其他免疫调节分子在调节肺孢子虫感染中的作用。我们开发了一种实时 PCR 检测方法，可在较宽的动态范围内定量肺孢子虫，目前正在检查健康动物的肺孢子虫感染，以更好地了解正常宿主的免疫反应。使用微阵列，我们已经能够识别健康小鼠和免疫缺陷小鼠在肺孢子虫感染期间差异表达的基因；大多数差异表达基因与免疫系统有关。希望这些研究能够深入了解健康宿主中控制肺孢子虫感染的关键机制，并可能提供增加肺孢子虫清除或减少可能导致缺氧的炎症的机制。