Interleukin-10 in acute respiratory virus infection

肺部炎症和损伤是病毒感染的常见（在某些情况下是致命的）结果 呼吸道感染呼吸道病毒感染引发宿主先天和后天免疫系统的协调反应， 适应性免疫系统宿主反应对于病毒清除和恢复是必不可少的，但也是一种免疫反应。 可能伴随病毒清除的肺损伤的重要原因。最近的相关例子 是在人类感染SARS冠状病毒时观察到的免疫介导的肺部炎症/损伤 和H5 N1禽流感病毒。项目1的长期目标是定义和描述 先天性免疫系统细胞（即树突细胞、单核细胞/巨噬细胞、NK细胞）之间的相互作用 和适应性免疫效应T淋巴细胞（Tej）在病毒清除过程中，并在控制 实验性病毒感染呼吸道期间的炎症/损伤。 这种应用的基础是我们最近在A型小鼠模型中的意外发现。 流感感染时，抗病毒效应T细胞（CD 4 +Te和更显著CDS +Te）浸润 感染的肺在Te期间产生高水平的抗炎/调节细胞因子IL-10 对感染和病毒清除的反应。此外，我们发现，阻断Te-衍生的IL-1的作用， 在感染过程中导致肺部炎症增加和致命性损伤。我们的证据进一步 提示这种Te衍生的IL-10在控制肺部炎症/损伤水平中起着重要作用 由单核细胞浸润感染的肺部产生，以响应病毒感染和促炎症反应。 病毒免疫释放的介质（Te）。我们希望分析这种基因的表达和调控 IL-10和特别是Te-衍生的IL-10在感染的肺中的表达以及这种细胞因子对对照的影响 病毒清除和肺部炎症/损伤。项目1的目标是：1。为了评估细胞 IL-10的来源及其在流感病毒感染中的作用; 2.分析IL-10产生的调节， 流感期间的TE; 3.为了确定病毒感染对Te-衍生的IL-1产生的影响， 10.拟议的研究旨在补充项目2、3和4中正在进行的相关研究。

Pulmonary inflammation and injury is a frequent (and, in some instances, lethal) outcome of virus infections of the respiratory tract. Respiratory virus infection triggers a coordinated response from the host innate and adaptive immune systems. The host response is essential for virus clearance and recovery, but is also a significant cause of pulmonary injury that can accompany virus elimination. Relevant recent examples of this are the immune-mediated lung inflammation/injury observed in human infections with the SARS coronavirus and the H5N1 avian influenza viruses. The long-term goal of Project 1 is to define and characterize the interactions between cells of the innate immune system i.e. dendritic cells, monocyte/ macrophage, NK cells and adaptive immune effector T lymphocytes (Tej in the process of virus clearance and in the control of inflammation/injury during experimental virus infection of the respiratory tract. The foundation for this application is our recent and unexpected findings in the murine model of type A influenza infection that anti-viral effector T-cells (both CD4 +Te and more prominently CDS +Te) infiltrating the infected lungs produce high levels of the anti-inflammatory/regulatory cytokines IL-10 during the Te response to infection and virus elimination. Furthermore, we found that blocking the effect of Te-derived IL- 10 during infection results in increased pulmonary inflammation and lethal injury. Our evidence further suggests that this Te-derived IL-10 plays a central role in controlling the level of lung inflammation/injury produced by mononuclear cells infiltrating the infected lungs in response to virus infection and the proinflammatory mediators released by virus- immune (Te). We wish to analyze the expression and regulation of IL-10 and specifically Te-derived IL-10 in the infected lungs and the impact of this cytokine on the control of virus clearance and lung inflammation/injury. The aims of Project 1 are: 1. To evaluate the cellular sources and effects of IL-10 on influenza virus infection; 2. To analyze the regulation of IL-10 production by Te during influenza infection; 3. To determine the impact of viral infection on the production of Te-derived IL- 10. The proposed studies are designed to complement ongoing related studies in Projects 2, 3 and 4.