Susceptibility determinants to Legionella pneumophila infection in smokers

吸烟者嗜肺军团菌感染的易感性决定因素

• 批准号: 10374758
• 负责人: Amal O Amer
• 金额: $ 19.5万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-18 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374758
• 关键词: Achievement; Alveolar Macrophages; Bacteria; Bronchoalveolar Lavage; CRISPR/Cas technology; Cell Line; Cells; Cessation of life; Cigarette; Cytosine; DNA; DNA Methylation; Data; Disease; Disease Outbreaks; Elderly; Epigenetic Process; Gene Expression; Gene Expression Profile; Genes; Genomics; Human; Immune; Immunity; Individual; Infection; Innate Immune Response; Legionella; Legionnaires' Disease; Lentivirus; Life Cycle Stages; Literature; Lung; Measures; Methylation; Molecular; Morbidity - disease rate; Ohio; Outcome; Pathway Analysis; Pattern; Persons; Phagocytes; Pneumonia; Predisposition; Publications; Reporting; Research; Resolution; Risk; Sample Size; Sampling; Small Interfering RNA; Smoker; Smoking; Smoking History; Structure of parenchyma of lung; Testing; Time; Tobacco smoking behavior; Transcriptional Regulation; Transferase; Universities; Whole Blood; base; bisulfite sequencing; cigarette smoke; drinking water; epidemiology study; gene function; genome-wide analysis; high risk; insight; macrophage; methylomics; monocyte; mortality; non-smoker; novel; permissiveness; tobacco smoke exposure; transcriptome sequencing

Susceptibility determinants to Legionella pneumophila infection in smokers Abstract Legionella accounts for majority of drinking water-associated pneumonia outbreaks with high percentage of death. Legionella infection presents with a higher risk and worse outcome in the elderly, immune-compromised and smokers. Several epidemiological studies have demonstrated a strong association between tobacco smoking and an elevated risk of Legionella infection. However, the underlying mechanism is still unclear. To determine the mechanism by which smoking predisposes to Legionella infection, we will perform the following aims: Aim 1. Determine the methylomic and RNAseq profile of human alveolar macrophages from current smokers (>10 pack years) and non-smokers. Aim 2. Determine the function of genes with altered methylation and expression and identify those responsible for the increased susceptibility of macrophages to Legionella infection.

吸烟者嗜肺军团菌感染的易感性决定因素 抽象的 军团菌占饮用水相关肺炎爆发的大部分，其中比例很高 死亡。对于免疫功能低下的老年人来说，军团菌感染的风险更高，结果更差 和吸烟者。多项流行病学研究表明，烟草与烟草之间存在密切关联。 吸烟和军团菌感染的风险增加。然而，其根本机制仍不清楚。到 为了确定吸烟导致军团菌感染的机制，我们将执行以下操作 目标： 目标 1. 确定当前吸烟者的人类肺泡巨噬细胞的甲基组学和 RNAseq 谱 （>10包年）和非吸烟者。目标 2. 确定甲基化改变的基因的功能和 表达并确定那些导致巨噬细胞对军团菌敏感性增加的原因 感染。