Circulating exosomes induced by respiratory viral infections in lung transplant recipients activate cellular stress, innate immune pathways and epithelial to mesenchymal transition

Background: Chronic lung transplant rejection occurs in over 50% of lung transplant recipients and mechanism of chronic rejection is unknown. Evaluation of potential mechanism of exosomes from lung transplant recipients diagnosed with respiratory viral infection (RVI) in inducing chronic lung allograft dysfunction (CLAD). Method: Exosomes were isolated from lung transplant recipients followed by DNA and RNA isolation from exosomes. Cell signaling mechanisms were studied by co-culturing exosomes with human epithelial cells. Mice were immunized with exosomes and lung homogenates were studied for immune signaling proteins. Results: Exosomes from lung transplant recipients with RVI carry nucleic acids which are capable of inducing innate immune signaling, endoplasmic reticulum stress, and epithelial mesenchymal transition. Conclusion: Therefore, we propose that RVI can lead to induction of exosomes that initiate the process leading to CLAD in mice models. These novel findings identified the molecular mechanisms by which RVI increases the risk of CLAD.

Automated summary

The study found that exosomes from lung transplant recipients with respiratory viral infection contain nucleic acids capable of inducing innate immune signaling, endoplasmic reticulum stress, and epithelial mesenchymal transition. Therefore, the authors propose that respiratory viral infection may lead to the generation of exosomes that initiate the process of CLAD in mouse models. The novel findings identify the molecular mechanisms through which respiratory viral infection increases the risk of CLAD.