IMMUNOMODULATION DURING PULMONARY CRYPTOCOCCOSIS

肺隐球菌病期间的免疫调节

• 批准号: 6056513
• 负责人: JUNEANN W MURPHY
• 金额: $ 25.55万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6056513
• 关键词: CD28 molecule; CD95 molecule; Cryptococcus neoformans; MHC class II antigen; T lymphocyte; antigen presenting cell; apoptosis; cellular immunity; cryptococcosis; cytokine; immunoregulation; interleukin 10; interleukin 4; laboratory mouse; microorganism immunology; polymerase chain reaction; transforming growth factors; tumor necrosis factor alpha

Cryptococcosis is a mycotic disease that is acquired by inhalation of the ubiquitous yeast-like organism, Cryptococcus neoformans. The primary pulmonary disease can range from mild to severe depending on the host's immunological status. The goal is to identify the mechanisms by which the anticryptococcal responses are down- regulated. The specific aims are: 1) to assess the role of IL-10 and IL- 4 in down-regulation of the anticryptococcal CMI response in mice infected with C. neoformans isolate NU-2 or 184A; 2) to examine the temporal profile of TGF-beta and TNFalpha and determine if blocking the activity of either or both of these cytokines would alter the anticryptococcal CMI response; 3) to determine if leukocyte surface markers such as B7-1, B7-2, major histocompatibility complex (MHC) class II antigens (1-A and I-E) on antigen presenting cells and CD28 and CTLA-4 on CD4plus and CD8plus T lymphocytes are modulated and examine the potential for the changes to contribute to the deviation in the anticryptococcal CMI response in NU-2-infected mice; 4) to examine the role of Fas/FasL-mediated apoptosis in the regulation of the anticryptococcal CMI response in the NU-2 infected mice; and 5) to apply differential display polymerase chain reaction (DD-PCR) technology to establish differences in mRNAs inducted by an infection with NU-2 (modulated CMI response) compared to mRNAs induced by an infection with 184A (prolonged protective CMI response) in the mouse model.

隐球菌病是一种真菌疾病，通过吸入 这种无处不在的酵母状有机体，新生隐球菌。这个 原发肺部疾病可从轻微到严重不等，具体取决于 关于宿主的免疫状态。我们的目标是确定 抗隐球菌反应下调的机制- 受监管的。具体目的是：1)评估IL-10和IL-10的作用。 4下调小鼠对隐球菌的CMI反应 感染新城疫杆菌NU-2或184a株；2)检测 转化生长因子-β和肿瘤坏死因子α的时间分布及是否阻断 这两种细胞因子中的一种或两种的活性会改变 抗隐球菌CMI反应；3)确定白细胞表面 B7-1、B7-2、主要组织相容性复合体(MHC)等标志物 抗原提呈细胞和CD28上的II类抗原(1-A和I-E) CD4plus和CD8plus T淋巴细胞表面CTLA-4被调节 并研究这些变化可能会对 NU-2感染的小鼠对隐球菌CMI反应的偏差； 4)探讨Fas/FasL介导的细胞凋亡在血管内皮细胞凋亡中的作用 NU-2感染株对隐球菌CMI免疫应答的调节 5)差异显示聚合酶链式反应 (DD-PCR)技术建立不同基因诱导的mRNA 感染NU-2(调节的CMI反应)与 184a(长时间保护性CMI)感染诱导的mRNAs 反应)。