Alcohol-induced Dysbiosis and HIV-associated Pneumonia

酒精引起的生态失调和艾滋病毒相关肺炎

• 批准号: 10023920
• 负责人: JUDD E SHELLITO
• 金额: $ 17.46万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10023920
• 关键词: Address; Affect; Alcohol abuse; Alcohol consumption; Alcoholic Liver Diseases; Alcohols; Animals; Bacteria; Bacterial Pneumonia; Caring; Cell Count; Cell physiology; Cells; Chronic; Clinical; Data; Defect; Etiology; Foundations; Future; HIV; HIV Infections; HIV Seronegativity; Host Defense; Human; Immune; Immune response; Immunity; Immunoglobulin A; Immunoglobulins; Impairment; Infection; Inflammation; Injury; Intestinal Mucosa; Intestines; Klebsiella pneumoniae; Knowledge; Laboratories; Link; Lung; Lung infections; Lymphocyte; Mediating; Microbe; Modeling; Mucous Membrane; Mus; National Institute on Alcohol Abuse and Alcoholism; Outcome; Patients; Pneumococcal Pneumonia; Pneumonia; Population; Predisposition; Process; Risk; Role; Sampling; Secretory Immunoglobulin A; Severities; Streptococcus pneumoniae; T-Lymphocyte; Testing; Tissues; Translational Research; Work; Xenograft procedure; alcohol exposure; alcohol misuse; antiretroviral therapy; bacterial community; dysbiosis; experimental study; fecal transplantation; gut bacteria; gut microbes; gut microbiome; gut microbiota; gut-lung axis; high reward; high risk; human subject; immune activation; liver injury; lung injury; microbial; microbiome; microbiota; pathogen; pneumonia model; transplant model

ABSTRACT Both alcohol misuse and HIV infection increase the risk for bacterial pneumonia, but the explanation for this increased risk is unknown. Preliminary data from our laboratory implicate changes in the gut microbiome (dysbiosis). We hypothesize that host susceptibility to bacterial pneumonia in alcohol-misusing and HIV-infected subjects is mediated through intestinal dysbiosis and changes in sIgA coating of specific bacterial groups. We will study human subjects and use a unique fecal transplant model where human fecal samples are xenotransplanted into mice. There are 2 Specific Aims. SA1 will address dysbiotic sIgA-coated bacteria as they influence host responses to a lung infectious challenge. SA2 will investigate the Mucosal-Associated Invariant T (MAIT) cell population of as an immune link between alcohol-induced dysbiosis and impaired host defense against pneumonia. This project will uncover mechanisms through which changes in gut microflora influence host responses to pulmonary infection (the gut-lung axis) and will lead to new knowledge as to how alcohol and HIV infection impair immunity in the lung.

摘要 酒精滥用和HIV感染都会增加细菌性肺炎的风险，但对此的解释是， 增加的风险是未知的。我们实验室的初步数据表明肠道微生物组发生了变化 （生态失调）。我们推测，在酗酒和HIV感染者中， 受试者通过肠道生态失调和特定细菌群的sIgA包被的变化介导。我们 将研究人类受试者，并使用一种独特的粪便移植模型， 异种移植到小鼠体内。有两个具体目标。SA 1将解决sIgA包被细菌的生态失调问题，因为它们 影响宿主对肺部感染性攻击反应。SA 2将研究粘膜相关不变T （MAIT）细胞群体作为酒精诱导的生态失调和受损的宿主防御之间的免疫联系 对抗肺炎该项目将揭示肠道微生物菌群变化影响 宿主对肺部感染的反应（肠-肺轴），并将导致关于酒精和 艾滋病毒感染会损害肺部的免疫力。