Abstract
Introduction: The lung microbiota has distinct constituents depending on local inflammatory status. As yet, the direct implications of the lung microbiota in disease development is unknown. We hypothesized that the lung microbiota directly influences macrophage functionality and consequently long-term graft survival.
Methods: DNA and total RNA were isolated from bronchoalveolar lavages from 58 patients at 0.5-4 (short-term) or 6-24 (long-term) months post-transplantation. 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: A subset of samples displayed macrophage polarization, either with inflammation and immunoregulation (Polar1, 20.7%) or remodeling (Polar2, 10.3%) predominance. Compared to Polar2, Polar1 were most often enriched in either Firmicutes, Proteobacteria or Actinobacteria, were more frequently associated with infection (83.3% vs. 20.0%) and had higher neutrophil counts as an indication of inflammation (62.5% vs. 8.7%). In contrast, Polar2 displayed a 42.3-111.6-fold increase in expression of pro-remodeling genes (TIMP1, PDGF, fibronectin) and higher Bacteroidetes percentage (median 53.4% vs. 2.1%). While Polar1 originated from similar numbers of short- and long-term transplant recipients, Polar2 were almost exclusively from the latter group (94.1%).
Conclusions: Alveolar macrophage polarization in conjunction with microbiota composition reflects dynamic changes in lung transplant recipients. Longitudinal follow-up of patients with polarized samples will elucidate whether these conditions may predict a negative outcome for graft survival.
- © 2014 ERS
