Shenoy Meera K, Iwai Shoko, Lin Din L, Worodria William, Ayakaka Irene, Byanyima Patrick, Kaswabuli Sylvia, Fong Serena, Stone Stephen, Chang Emily, Davis J Lucian, Faruqi Ali Ahmad, Segal Mark R, Huang Laurence, Lynch Susan V
1 Division of Gastroenterology, Department of Medicine.
2 Biomedical Sciences Graduate Program.
Am J Respir Crit Care Med. 2017 Jan 1;195(1):104-114. doi: 10.1164/rccm.201603-0523OC.
The potential role of the airway microbiota in dictating immune responses and infection outcomes in HIV-associated pneumonia is largely unknown.
To investigate whether microbiologically and immunologically distinct subsets of patients with HIV and pneumonia exist and are related to mortality.
Bronchoalveolar lavage samples from Ugandan patients with HIV and pneumonia (n = 182) were obtained at study enrollment (following antibiotic treatment); patient demographics including 8- and 70-day mortality were collected. Lower airway bacterial community composition was assessed via amplification and sequencing of the V4 region of the 16S ribosomal RNA gene. Host immune response gene expression profiles were generated by quantitative polymerase chain reaction using RNA extracted from bronchoalveolar lavage fluid. Liquid and gas chromatography mass spectrometry was used to profile serum metabolites.
Based on airway microbiome composition, most patients segregated into three distinct groups, each of which were predicted to encode metagenomes capable of producing metabolites characteristically enriched in paired serum samples from these patients. These three groups also exhibited differences in mortality; those with the highest rate had increased ceftriaxone administration and culturable Aspergillus, and demonstrated significantly increased induction of airway T-helper cell type 2 responses. The group with the lowest mortality was characterized by increased expression of T-cell immunoglobulin and mucin domain 3, which down-regulates T-helper cell type 1 proinflammatory responses and is associated with chronic viral infection.
These data provide evidence that compositionally and structurally distinct lower airway microbiomes are associated with discrete local host immune responses, peripheral metabolic reprogramming, and different rates of mortality.
气道微生物群在决定HIV相关肺炎的免疫反应和感染结果方面的潜在作用在很大程度上尚不清楚。
研究HIV合并肺炎患者在微生物学和免疫学上是否存在不同亚组，以及这些亚组是否与死亡率相关。
在研究入组时（接受抗生素治疗后）获取乌干达HIV合并肺炎患者（n = 182）的支气管肺泡灌洗样本；收集患者人口统计学数据，包括8天和70天死亡率。通过对16S核糖体RNA基因V4区域进行扩增和测序来评估下呼吸道细菌群落组成。使用从支气管肺泡灌洗液中提取的RNA，通过定量聚合酶链反应生成宿主免疫反应基因表达谱。采用液相色谱-质谱联用和气相色谱-质谱联用技术分析血清代谢物。
基于气道微生物组组成，大多数患者分为三个不同的组，预计每组编码的宏基因组能够产生在这些患者配对血清样本中特征性富集的代谢物。这三组在死亡率方面也存在差异；死亡率最高的组头孢曲松使用量增加且可培养曲霉菌存在，气道2型辅助性T细胞反应诱导显著增加。死亡率最低的组特征是T细胞免疫球蛋白和粘蛋白结构域3表达增加，该蛋白可下调1型辅助性T细胞促炎反应，且与慢性病毒感染相关。
这些数据提供了证据，表明在组成和结构上不同的下呼吸道微生物群与离散的局部宿主免疫反应、外周代谢重编程以及不同的死亡率相关。
