Interleukin-10 in acute respiratory virus infection

肺部炎症和损伤是病毒感染的常见结果(在某些情况下甚至是致命的) 对呼吸道的影响。呼吸道病毒感染触发宿主先天和 适应性免疫系统。宿主响应对于病毒清除和恢复至关重要，但也是一种 伴随病毒清除而导致肺损伤的重要原因。最近的相关例子 人类感染SARS冠状病毒时是否观察到免疫介导的肺部炎症/损伤 以及H5N1禽流感病毒。项目1的长期目标是定义和描述 天然免疫系统中树突状细胞、单核/巨噬细胞、NK细胞之间的相互作用 和获得性免疫效应T淋巴细胞(Tej)在病毒清除和控制过程中的作用 呼吸道实验性病毒感染期间的炎症/损伤。 这一应用的基础是我们最近在A型小鼠模型中出人意料的发现 流感感染，抗病毒效应T细胞(包括CD4+Te和更突出的CDS+Te)渗透 在Te过程中，感染的肺产生高水平的抗炎/调节细胞因子IL-10 对感染和病毒清除的反应。此外，我们还发现阻断Te来源的IL-1的作用。 10感染期间会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来源的IL-10在控制肺部炎症/损伤水平中起核心作用 由单个核细胞渗入受感染的肺以应对病毒感染和促炎反应而产生 病毒免疫(Te)释放的介体。我们想要分析的是表达和调控 IL-10和特异性Te来源的IL-10在感染肺中的表达及该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.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的产生调节 确定病毒感染对Te来源的IL-2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.