BackgroundHomeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling.ObjectiveThis study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation.MethodsMicrobiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture.ResultsWe identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition.ConclusionsHost-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome.

Our data suggest that BBB stabilization by IFN-beta-1a may contribute to its beneficial effects in the treatment of MS. A human in vitro BBB model might be useful as bioassay for testing the treatment efficacy of drugs in MS.

The leukocyte inhibition module downregulated cardiopulmonary bypass-related neutrophil activity and thus might be beneficial in cardiac surgery and other clinical settings with unappreciated neutrophil activation.

Highlights d Pelvic brooding induces tissue-specific changes in gene expression d Inflammatory signaling characterizes transcriptome of the egg-anchoring plug d Similar to embryo implantation, the plug likely evolved from an inflammatory response d Mammalian placenta genes were independently co-opted into the plug

Recently, we showed that the arterial in-line application of the leukocyte inhibition module (LIM) within the heart-lung machine limits overshooting leukocyte activity and cardiac tissue damage. Moreover, significantly better cardiac function was found in an experimental animal model when LIM was used. In the meantime, the first promising clinical data exist. LIM has to be regarded as an essential tool in extracorporeal circulation, in the future, to improve postoperative clinical outcome and to reduce costs. This review summarizes the biological background of LIM and the current experience obtained in experimental models and clinical studies.