Investigating the role of altered lung microbiome in fueling Th17 mediated airway inflammation in COPD among HIV-infected individual

研究肺部微生物组改变在 HIV 感染者 COPD 中促进 Th17 介导的气道炎症的作用

• 批准号: 10535320
• 负责人: Alex Kayongo
• 金额: $ 15万
• 依托单位: MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10535320
• 关键词: Adult; Africa South of the Sahara; Airway Disease; Antigen Presentation; Applications Grants; Attention; Automobile Driving; Biological Assay; Bronchoalveolar Lavage; Bronchoscopy; CD4 Lymphocyte Count; Case-Control Studies; Cells; Chronic; Chronic Obstructive Pulmonary Disease; Clinic; Control Groups; Cytometry; Data; Dendritic Cells; Distal; Exhibits; Frequencies; General Population; Genes; Genus staphylococcus; HIV; High Prevalence; Immune; Immune response; Improve Access; Individual; Inflammation; Inflammatory; Inflammatory Response; Interferons; Interleukin-1; Interleukin-17; Life Expectancy; Link; Longevity; Lung; Lung infections; Mediating; Metagenomics; Morbidity - disease rate; Outcome; Paralysed; Participant; Pathogenesis; Pathway interactions; Persons; Population; Porphyromonas; Prevalence; Prevotella; Production; Proteins; Publishing; Pulmonary Inflammation; Regulatory T-Lymphocyte; Reporting; Ribosomal DNA; Role; Rural; Sampling; Sputum; Stains; Students; Surface; Survivors; Testing; Time; Tissue-Specific Gene Expression; Transforming Growth Factor beta; Uganda; Ursidae Family; Veillonella; Viral Load result; Work; airway immune response; airway inflammation; antiretroviral therapy; base; case control; cohort; cytokine; density; design; differential expression; dysbiosis; experience; high dimensionality; host-microbe interactions; insight; low and middle-income countries; lung microbiome; microbial; microorganism; mortality; peripheral blood; rRNA Genes; respiratory microbiome; response; single-cell RNA sequencing

Abstract Chronic obstructive pulmonary disease (COPD) is increasing in prevalence among people living with HIV (PLWH) as widespread use of Antiretroviral Therapy (ART) has increased longevity in this population. In rural Ugandan ART clinics, we report COPD prevalence of 6.22%. Currently, it’s not fully known what drives chronic lung inflammation in PLWH despite being virologically suppressed on ART. There is need to explore factors driving chronic airway inflammation among PLWH. Airway microbiome has been implicated in the pathogenesis of COPD. Using 16S ribosomal RNA gene (rDNA) sequencing on induced sputum samples from 200 adults with equal numbers of participants by HIV and COPD status in our rural Ugandan cohort, we show that among PLWH, airway enrichment with Staphylococcus spp as well as depletion of Pseudopropionibacterium and Porphyromonas spp are associated with COPD. Currently, we don’t fully understand how such genera drive chronic airway inflammation. In this study, we will determine the association between lung microbiome and immune responses (particularly Th17/Treg responses) in the distal airways of PLWH with COPD in a viremically controlled Ugandan cohort using BAL samples. We hypothesize that: (i) a Th17-driven pro-inflammatory immune response predominates in the distal airways of PLWH with COPD and (ii) specific distal airway microbial species (signatures) are associated with Th17-immune response among PLHW with COPD. In this study, we will determine (1): the distal airway immune profile among individuals with HIV and COPD in Uganda and (2) the association between lung microbiome and distal airway immune responses using BAL samples.

摘要 慢性阻塞性肺疾病（COPD）在艾滋病毒感染者中的流行率正在上升 艾滋病毒携带者（PLWH）作为广泛使用的抗逆转录病毒疗法（ART）增加了这一人群的寿命。农村 乌干达ART诊所，我们报告COPD患病率为6.22%。目前，还不完全清楚是什么导致慢性 尽管ART治疗后病毒学抑制，但PLWH患者的肺部炎症仍存在。 导致PLWH中的慢性气道炎症。呼吸道微生物组与 COPD的发病机制。使用16 S核糖体RNA基因（rDNA）测序对来自 在乌干达农村队列中，我们显示了200名成年人，按HIV和COPD状态划分的参与者人数相等， 在PLWH中，呼吸道葡萄球菌属的富集以及 假丙酸杆菌属和卟啉单胞菌属与COPD相关。目前，我们还没有完全 了解这些细菌如何驱动慢性气道炎症。在这项研究中，我们将确定 肺微生物组和免疫应答（特别是Th 17/Treg应答）之间的关系 使用BAL样本的病毒对照乌干达队列中的PLWH伴COPD。我们假设：（i）a Th 17驱动的促炎性免疫应答在PLWH伴COPD的远端气道中占主导地位， (ii)特异性远端气道微生物种类（特征）与Th 17免疫应答相关， PLHW伴COPD。在本研究中，我们将确定（1）：患有以下疾病的个体的远端气道免疫概况： 乌干达的HIV和COPD以及（2）肺部微生物组与远端气道免疫之间的相关性 使用BAL样品的响应。