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Distal airway microbiome is associated with immunoregulatory myeloid cell responses in lung transplant recipients.

ABSTRACT: 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.

SUBMITTER: Sharma NS

PROVIDER: S-EPMC5893420 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Distal airway microbiome is associated with immunoregulatory myeloid cell responses in lung transplant recipients.

Sharma Nirmal S NS Wille Keith M KM Athira S S Zhi Degui D Hough Kenneth P KP Diaz-Guzman Enrique E Zhang Kui K Kumar Ranjit R Rangarajan Sunad S Eipers Peter P Wang Yong Y Srivastava Ritesh K RK Rodriguez Dager Jose Vicente JV Athar Mohammad M Morrow Casey C Hoopes Charles W CW Chaplin David D DD Thannickal Victor J VJ Deshane Jessy S JS

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 20170715

<h4>Background</h4>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.<h4>Methods</h4>Bronchoalveolar lavage (BAL) and simultane ...[more]

PMID: 28756121

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Project description:Infection and rejection are the two most common complications after lung transplantation (LT) and are associated with increased morbidity and mortality. We aimed to examine the association between the airway microbiota and infection and rejection in lung transplant recipients (LTRs). Here, we collected 181 sputum samples (event-free, n = 47; infection, n = 103; rejection, n = 31) from 59 LTRs, and performed 16S rRNA gene sequencing to analyze the airway microbiota. A significantly different airway microbiota was observed among event-free, infection and rejection recipients, including microbial diversity and community composition. Nineteen differential taxa were identified by linear discriminant analysis (LDA) effect size (LEfSe), with 6 bacterial genera, Actinomyces, Rothia, Abiotrophia, Neisseria, Prevotella, and Leptotrichia enriched in LTRs with rejection. Random forest analyses indicated that the combination of the 6 genera and procalcitonin (PCT) and T-lymphocyte levels showed area under the curve (AUC) values of 0.898, 0.919 and 0.895 to differentiate between event-free and infection recipients, event-free and rejection recipients, and infection and rejection recipients, respectively. In conclusion, our study compared the airway microbiota between LTRs with infection and acute rejection. The airway microbiota, especially combined with PCT and T-lymphocyte levels, showed satisfactory predictive efficiency in discriminating among clinically stable recipients and those with infection and acute rejection, suggesting that the airway microbiota can be a potential indicator to differentiate between infection and acute rejection after LT. IMPORTANCE Survival after LT is limited compared with other solid organ transplantations mainly due to infection- and rejection-related complications. Differentiating infection from rejection is one of the most important challenges to face after LT. Recently, the airway microbiota has been reported to be associated with either infection or rejection of LTRs. However, fewer studies have investigated the relationship between airway microbiota together with infection and rejection of LTRs. Here, we conducted an airway microbial study of LTRs and analyzed the airway microbiota together with infection, acute rejection, and clinically stable recipients. We found different airway microbiota between infection and acute rejection and identify several genera associated with each outcome and constructed a model that incorporates airway microbiota and clinical parameters to predict outcome. This study highlighted that the airway microbiota was a potential indicator to differentiate between infection and acute rejection after LT.

Dataset Information

Distal airway microbiome is associated with immunoregulatory myeloid cell responses in lung transplant recipients.

Publications

Distal airway microbiome is associated with immunoregulatory myeloid cell responses in lung transplant recipients.

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