Chronic alcohol and pulmonary immunity

慢性酒精中毒增加了呼吸道疾病和感染的发病率和严重程度。 事实上，酗酒者与非酗酒者相比， 在细菌性肺炎期间。虽然人们对慢性酒精在 增加呼吸道细菌感染的严重程度，但对如何增加呼吸道细菌感染的严重程度了解得更少。 慢性乙醇（EtOH）消耗改变了肺部病毒感染的严重性。有趣的是， 我们的初步研究表明，慢性乙醇会增加 甲型流感病毒感染。我们的研究结果进一步表明，疾病严重程度的增加可能 与呼吸道树突状细胞以及流感特异性CDS-T的缺陷或改变有关 细胞反应。鉴于目前流行病和大流行性流感的威胁， 了解慢性酒精中毒者肺部适应性免疫反应中的病变 可能会导致提高对这种重要人类病原体的免疫力的方法。因此我们 长期目标是确定慢性EtOH在呼吸适应性内诱导什么样的病变， 免疫反应在本申请中，我们将继续使用Meadow-Cook慢性EtOH 模型以及我们的流感病毒感染小鼠模型，以确定EtOH相关 发生在呼吸道树突细胞和流感特异性CDS T细胞内的病变。我们的中央 一种假说认为，呼吸道树突状细胞功能和CDS T细胞应答的缺陷 是慢性EtOH中观察到的流感病毒感染严重程度增加的原因 小鼠我们提出了以下具体目标：1）确定在静息状态下的病变 慢性EtOH小鼠的肺免疫系统2）测定流感病毒的致病性- 3）确定DC在慢性EtOH感染中的作用， 4）流感特异性CD 8 T细胞的比率的测定 慢性EtOH小鼠中增强疾病的免疫力。这一建议不仅将界定缺陷 慢性EtOH在呼吸道病毒感染期间产生肺部适应性免疫， 还应该增加我们对其他（细菌/真菌）呼吸道疾病免疫力的理解。 感染.此外，从该提案中获得的见解可能会建议 在这些疾病期间恢复和/或增强慢性酒精中毒者免疫力的方法。

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.