Host-Microbial Interactions in Idiopathic Pulmonary Fibrosis
Host-Microbial Interactions in Idiopathic Pulmonary Fibrosis
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DOI：
10.1164/rccm.201607-1408oc
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发表时间：
2017-06-15
影响因子：
24.7
通讯作者：
Maher, Toby M.
中科院分区：
文献类型：
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作者：
Molyneaux, Philip L.;Willis-Owen, Saffron A. G.;Maher, Toby M.
理由：呼吸道微生物组的变化与特发性肺纤维化 (IPF) 的疾病进展相关。宿主对呼吸道微生物群反应的作用仍不清楚。目的：探索 IPF 中宿主微生物的相互作用。方法：前瞻性招募 60 名诊断为 IPF 的患者以及 20 名匹配的对照受试者。受试者接受支气管肺泡灌洗（BAL），所有受试者在基线时将外周全血收集到 PAXgene 管中。对于患有 IPF 的受试者，在 1、3 和 6 个月以及（如果还活着）1 年时采集了额外的样本。使用 Affymetrix Human Gene 1.1 ST 阵列生成基因表达谱。测量和主要结果：通过基因表达数据的网络分析，我们确定了与 IPF 诊断、BAL 细菌负荷（通过 16S 定量聚合酶链式反应测定）和特定微生物操作分类单位以及灌洗液和外周血中性粒细胞增多密切相关的两个基因模块。这些模块中参与宿主防御反应的基因包括 NLRC4、PGLYRP1、MMP9 和 DEFA4。该模块还包含两个编码特定抗菌肽的基因（SLPI 和 CAMP）。许多这些特定转录本与生存相关，并在经历疾病进展的受试者中显示出纵向过度表达，进一步加强了转录本与疾病的关系。结论：宿主转录组和微生物特征的综合分析表明，宿主对改变或更丰富的微生物组的存在有明显的反应。这些反应在纵向随访中仍然升高，表明下呼吸道细菌群落可能对 IPF 中重复性肺泡损伤起到持续刺激作用。
Rationale: Changes in the respiratory microbiome are associated with disease progression in idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome remains unknown.Objectives: To explore the host microbial interactions in IPF.Methods: Sixty patients diagnosed with IPF were prospectively enrolled together with 20 matched control subjects. Subjects underwent bronchoalveolar lavage (BAL), and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For subjects with IPF, additional samples were taken at 1, 3, and 6 months and (if alive) 1 year. Gene expression profiles were generated using Affymetrix Human Gene 1.1 ST arrays.Measurements and Main Results: By network analysis of gene expression data, we identified two gene modules that strongly associated with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative polymerase chain reaction), and specific microbial operational taxonomic units, as well as with lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defense response include NLRC4, PGLYRP1, MMP9, and DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal overexpression in subjects experiencing disease progression, further strengthening the relationship of the transcripts with disease.Conclusions: Integrated analysis of the host transcriptome and microbial signatures demonstrated an apparent host response to the presence of an altered or more abundant microbiome. These responses remained elevated in longitudinal follow-up,, suggesting that the bacterial communities of the lower airways may act as persistent stimuli for repetitive alveolar injury in IPF.