Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation
Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation
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DOI：
10.1164/rccm.201512-2424oc
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发表时间：
2016-11-15
影响因子：
24.7
通讯作者：
Nicod, Laurent P.
中科院分区：
文献类型：
--
作者：
Bernasconi, Eric;Pattaroni, Celine;Nicod, Laurent P.
理由：在肺移植受者中，移植物的长期存活依赖于炎症和组织重塑的控制，以维持移植物功能并避免慢性肺同种异体移植物功能障碍。尽管临床实践的进步提高了移植的成功率，但维持炎症和重塑之间平衡的机制在很大程度上尚不清楚。 目的： 评估移植肺中宿主微生物的相互作用是否决定气道的免疫张力，从而影响移植物的存活。 方法： 从 112 名肺移植患者的 203 份支气管肺泡灌洗液中分离微生物群 DNA 和宿主总 RNA。使用 16S 核糖体 RNA 分析确定微生物群组成，并使用实时定量聚合酶链反应对涉及原型巨噬细胞功能的一组基因的表达进行定量。测量和主要结果：我们表明，肺部微生物群的特征与不同的先天细胞基因表达谱相一致。尽管非极化激活与由促炎性细菌（例如葡萄球菌和假单胞菌）和低刺激性细菌（例如普雷沃氏菌和链球菌）之间的平衡组成的细菌群落相关，但“炎症”和“重塑”特征与细菌生态失调有关。机制测定提供了直接证据，表明细菌生态失调可能导致巨噬细胞炎症或重塑，而平衡的微生物群落则维持稳态。结论：细菌群落和先天免疫细胞之间的串扰可能决定移植肺的功能，为干预策略提供新的途径。
Rationale: In lung transplant recipients, long-term graft survival relies on the control of inflammation and tissue remodeling to maintain graft functionality and avoid chronic lung allograft dysfunction. Although advances in clinical practice have improved transplant success, the mechanisms by which the balance between inflammation and remodeling is maintained are largely unknown.Objectives: To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival.Methods: Microbiota DNA and host total RNA were isolated from 203 bronchoalveolar lavages obtained from 112 patients post-lung transplantation. Microbiota composition was determined using 16S ribosomal RNA analysis, and expression of a set of genes involved in prototypic macrophage functions was quantified using real-time quantitative polymerase chain reaction.Measurements and Main Results: We show that the characteristics of the pulmonary microbiota aligned with distinct innate cell gene expression profiles. Although a nonpolarized activation was associated with bacterial communities consisting of a balance between proinflammatory (e.g., Staphylococcus and Pseudomonas) and low stimulatory (e.g., Prevotella and Streptococcus) bacteria, "inflammatory" and "remodeling" profiles were linked to bacterial dysbiosis. Mechanistic assays provided direct evidence that bacterial dysbiosis could lead to inflammatory or remodeling profiles in macrophages, whereas a balanced microbial community maintained homeostasis.Conclusions: The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.