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

摘要 慢性阻塞性肺疾病(COPD)在艾滋病毒携带者中的患病率正在上升 (PLWH)，因为抗逆转录病毒疗法(ART)的广泛使用延长了这一人群的寿命。在农村 乌干达ART诊所，我们报告COPD患病率为6.22%。目前，人们还不完全清楚是什么原因导致了慢性 PLWH的肺部炎症，尽管在ART的病毒学上被抑制。有必要探索这些因素 在PLWH中驱动慢性呼吸道炎症。呼吸道微生物群被认为与 慢性阻塞性肺疾病的发病机制。用16S核糖体RNA基因(RDNA)对沙门氏菌诱导痰标本进行测序 我们显示，在我们乌干达农村队列中，有200名成年人的艾滋病毒和慢性阻塞性肺病的参与者数量相等 在PLWH中，呼吸道葡萄球菌浓集，以及 假丙酸杆菌和卟啉单胞菌与慢性阻塞性肺疾病有关。目前，我们还没有完全 了解这些属是如何推动慢性呼吸道炎症的。在这项研究中，我们将确定这种关联 肺微生物群与肺远端呼吸道免疫反应(尤其是Th17/Treg反应)之间的关系 使用BAL样本在病毒控制的乌干达队列中检测PLWH和COPD。我们假设：(I)a Th17驱动的促炎免疫反应在慢性阻塞性肺疾病和慢性阻塞性肺疾病患者的PLWH远端气道中占主导地位 (Ii)特定的呼吸道远端微生物种类(特征)与Th17免疫反应有关 慢性阻塞性肺疾病患者的PLHW。在这项研究中，我们将确定(1)：患有以下疾病的个体的远端呼吸道免疫状况 乌干达的HIV和COPD以及(2)肺微生物群和远端呼吸道免疫之间的关系 使用BAL样本进行回复。

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.