Sharma Nirmal S, Wille Keith M, Athira S, Zhi Degui, Hough Kenneth P, Diaz-Guzman Enrique, Zhang Kui, Kumar Ranjit, Rangarajan Sunad, Eipers Peter, Wang Yong, Srivastava Ritesh K, Rodriguez Dager Jose Vicente, Athar Mohammad, Morrow Casey, Hoopes Charles W, Chaplin David D, Thannickal Victor J, Deshane Jessy S
Division of Pulmonary Allergy & Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Cognub Decision Solutions, Kerala, India.
J Heart Lung Transplant. 2017 Jul 15. doi: 10.1016/j.healun.2017.07.007.
Long-term survival of lung transplant recipients (LTRs) is limited by the occurrence of bronchiolitis obliterans syndrome (BOS). Recent evidence suggests a role for microbiome alterations in the occurrence of BOS, although the precise mechanisms are unclear. In this study we evaluated the relationship between the airway microbiome and distinct subsets of immunoregulatory myeloid-derived suppressor cells (MDSCs) in LTRs.
Bronchoalveolar lavage (BAL) and simultaneous oral wash and nasal swab samples were collected from adult LTRs. Microbial genomic DNA was isolated, 16S rRNA genes amplified using V4 primers, and polymerase chain reaction (PCR) products sequenced and analyzed. BAL MDSC subsets were enumerated using flow cytometry.
The oral microbiome signature differs from that of the nasal, proximal and distal airway microbiomes, whereas the nasal microbiome is closer to the airway microbiome. Proximal and distal airway microbiome signatures of individual subjects are distinct. We identified phenotypic subsets of MDSCs in BAL, with a higher proportion of immunosuppressive MDSCs in the proximal airways, in contrast to a preponderance of pro-inflammatory MDSCs in distal airways. Relative abundance of distinct bacterial phyla in proximal and distal airways correlated with particular airway MDSCs. Expression of CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP), an endoplasmic (ER) stress sensor, was increased in immunosuppressive MDSCs when compared with pro-inflammatory MDSCs.
The nasal microbiome closely resembles the microbiome of the proximal and distal airways in LTRs. The association of distinct microbial communities with airway MDSCs suggests a functional relationship between the local microbiome and MDSC phenotype, which may contribute to the pathogenesis of BOS.
细支气管闭塞综合征（BOS）的发生限制了肺移植受者（LTRs）的长期生存。近期证据表明微生物群改变在BOS的发生中起作用，尽管确切机制尚不清楚。在本研究中，我们评估了LTRs气道微生物群与免疫调节性髓源性抑制细胞（MDSCs）不同亚群之间的关系。
从成年LTRs收集支气管肺泡灌洗（BAL）样本以及同时收集口腔冲洗液和鼻拭子样本。分离微生物基因组DNA，使用V4引物扩增16S rRNA基因，并对聚合酶链反应（PCR）产物进行测序和分析。使用流式细胞术对BAL中的MDSC亚群进行计数。
口腔微生物群特征不同于鼻腔、近端和远端气道微生物群，而鼻腔微生物群更接近气道微生物群。个体受试者的近端和远端气道微生物群特征是不同的。我们在BAL中鉴定出MDSC的表型亚群，近端气道中免疫抑制性MDSC比例较高，而远端气道中促炎性MDSC占优势。近端和远端气道中不同细菌门的相对丰度与特定的气道MDSC相关。与促炎性MDSC相比，免疫抑制性MDSC中内质网（ER）应激传感器CCAAT/增强子结合蛋白（C/EBP）-同源蛋白（CHOP）的表达增加。
鼻腔微生物群与LTRs近端和远端气道的微生物群非常相似。不同微生物群落与气道MDSC的关联表明局部微生物群与MDSC表型之间存在功能关系，这可能有助于BOS的发病机制。
