Abstract
Introduction: The transplanted lung can be viewed as an ecological habitat, whose equilibrium conditions graft fate. Owing to the plasticity of alveolar macrophage activation and pulmonary microbiota composition, we hypothesized that the analysis of these airway constituents will help characterize lung ecology post-transplantation (Tx).
Methods: DNA and total RNA were isolated from 184 bronchoalveolar lavages obtained from 110 patients between 0.5 and 24 months post-lung Tx. Expression of a set of genes involved in prototypic macrophage functions was quantified using RT-qPCR. Microbiota composition at phylum level was determined using 16S rDNA amplification.
Results: We found a majority of samples with either type 1 (M1, 12%) or type 2 (M2, 53%) polarization. In comparison to non-polarized samples and M2, M1 displayed a 2.9 and 11.6-fold increase in TNF and COX-2 expression, respectively, reflecting inflammation. M2 showed a 3.2-fold increase in PDGFD expression and a 2.6-fold higher TIMP1 to MMP12 expression ratio indicating tissue remodeling. While the percentage of M1 was maximal at 3 months post-lung Tx (23%), M2 culminated at 12 months (57.5%) suggesting different time-dependent ecological constraints linked to these activation profiles. The composition of lung microbiota was found to be dominated by different groups of bacteria depending on the type of macrophage activation and to show corroborating temporal changes.
Conclusions: Characterization of alveolar macrophage polarization and microbiota composition, which jointly highlight dynamic changes in lung ecology, provides a new monitoring tool in the longitudinal follow-up of lung transplant recipients.
- Copyright ©ERS 2015