Chronic alcohol and pulmonary immunity

慢性酒精中毒会增加呼吸道疾病和感染的发生率和严重性。 事实上，与非酗酒者相比，酗酒者的死亡率和发病率都有所增加。 在细菌性肺炎期间。虽然很多人都知道慢性酒精在其中扮演的角色 增加呼吸道细菌感染的严重程度，更少人知道如何 慢性乙醇(Etoh)消费改变了肺部病毒感染的严重程度。有趣的是， 我们的初步研究表明，慢性无水乙醇会增加糖尿病的发病率和死亡率。 甲型流感病毒感染。此外，我们的结果表明，疾病严重性的增加可能 与呼吸道树突状细胞和流感特异性CDS T的缺陷或改变有关 细胞反应。鉴于目前疫情和大流行性流感的威胁， 对慢性酒精中毒患者肺获得性免疫反应损害的认识 可能导致方法来提高对这种重要的人类病原体的免疫力。因此我们的 长期目标是确定慢性无水乙醇在呼吸适应性中引起的损害 免疫反应。在此应用程序中，我们将继续使用Meadow-Cook Chronic Etoh 以及我们的小鼠流感病毒感染模型来确定与EtoH相关的 发生在呼吸道树突状细胞和流感特异性CDS T细胞内的病变。我们的中央 假设呼吸道树突状细胞功能和CDS T细胞反应均有缺陷 对观察到的慢性Etoh流感病毒感染严重程度的增加负责 老鼠。我们提出以下具体目标：1)确定静息状态下的病变 慢性无水乙醇小鼠的肺免疫系统2)流感致病性的测定 慢性无水乙醇小鼠感染3)树突状细胞在慢性无水乙醇增强中的作用 流感相关病理4)流感特异性CDS T细胞的测定 慢性乙醇中毒小鼠疾病增强的免疫力。这项提议不仅定义了缺陷 慢性乙醇在呼吸道病毒感染期间产生肺适应性免疫，但 也应该增加我们对其他(细菌/真菌)呼吸道免疫的理解 感染。此外，从这项提案中学到的见解有可能表明 恢复和/或提高慢性酗酒者在这些疾病期间的免疫力的方法。

Chronic alcoholism increases the incidence and severity of respiratory diseases and infections. Indeed, alcoholics compared to non-alcoholic individuals have increased mortality and morbidity during bacterialpneumonias. While much is known about the role that chronic alcohol plays in increasing the severity of respiratory bacterial infections, much less is understood about how chronic ethanol (EtOH) consumption alters the severity of pulmonary virus infections. Interestingly, our preliminary studies indicate that chronic EtOH increases both the morbidity and mortality of influenza A virus infections. Further our results suggest that the increased severity of disease may relate to defects or alterations in both respiratory dendritic cells as well as influenza-specific CDS T cell responses. Given the current threat of both epidemic and pandemic influenza a better understanding of the lesions within the pulmonary adaptive immune response in chronic alcoholics could lead to methodologies to boost immunity to this Important human pathogen. Therefore our long-range goal is to determine what lesions chronic EtOH induces within the respiratory adaptive immune response. Within this application we will continue to use the Meadow-Cook chronic EtOH model as well as our mouse models of influenza virus infection to determine the EtOH associated lesions that occur within respiratory dendritic cells and influenza-specific CDS T cells. Our central hypothesis is that defects within both respiratory dendritic cell function and CDS T cell responses are responsible for the observed increased severity of influenza virus infections in chronic EtOH mice. We propose the following Specific Aims: 1) Determination of the lesion within the resting pulmonary immune system of chronic EtOH mice 2) Determination of the pathogenicity of influenza- infection in chronic EtOH mice 3) Detennination of the role of DC in chronic EtOH enhanced influenza-associated pathology 4) Determination of the rple of influenza-specific CDS T cell immunity in enhanced disease in chronic EtOH mice. This proposal will not only define the defects that chronic EtOH creates In pulmonary adaptive immunity during respiratory virus infections but should also increase our understanding of immunity during other (bacterial/fungal) respiratory infections. Furthermore, the insights learned from this proposal hold the potential to suggest methodologies to restore and/or boost immunity in chronic alcoholics during these diseases.