Respiratory viral infection in lung transplantation induces exosomes that trigger chronic rejection

Muthukumar Gunasekaran, Sandhya Bansal, Ranjithkumar Ravichandran, Monal Sharma, Sudhir Perincheri, Francisco Rodriguez, Ramsey Hachem, Cynthia E. Fisher, Ajit P. Limaye, Ashraf Omar, Michael A. Smith, Ross M. Bremner, Thalachallour Mohanakumar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


BACKGROUND: Respiratory viral infections can increase the risk of chronic lung allograft dysfunction after lung transplantation, but the mechanisms are unknown. In this study, we determined whether symptomatic respiratory viral infections after lung transplantation induce circulating exosomes that contain lung-associated self-antigens and assessed whether these exosomes activate immune responses to self-antigens. METHODS: Serum samples were collected from lung transplant recipients with symptomatic lower- and upper-tract respiratory viral infections and from non-symptomatic stable recipients. Exosomes were isolated via ultracentrifugation; purity was determined using sucrose cushion; and presence of lung self-antigens, 20S proteasome, and viral antigens for rhinovirus, coronavirus, and respiratory syncytial virus were determined using immunoblot. Mice were immunized with circulating exosomes from each group and resulting differential immune responses and lung histology were analyzed. RESULTS: Exosomes containing self-antigens, 20S proteasome, and viral antigens were detected at significantly higher levels (p < 0.05) in serum of recipients with symptomatic respiratory viral infections (n = 35) as compared with stable controls (n = 32). Mice immunized with exosomes from recipients with respiratory viral infections developed immune responses to self-antigens, fibrosis, small airway occlusion, and significant cellular infiltration; mice immunized with exosomes from controls did not (p < 0.05). CONCLUSIONS: Circulating exosomes isolated from lung transplant recipients diagnosed with respiratory viral infections contained lung self-antigens, viral antigens, and 20S proteasome and elicited immune responses to lung self-antigens that resulted in development of chronic lung allograft dysfunction in immunized mice.

Original languageEnglish (US)
Pages (from-to)379-388
Number of pages10
JournalJournal of Heart and Lung Transplantation
Issue number4
StatePublished - Apr 2020
Externally publishedYes


  • antibodies
  • antigens
  • chronic rejection
  • exosomes
  • graft rejection
  • lung transplantation
  • respiratory viral infection

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Transplantation
  • Pulmonary and Respiratory Medicine
  • Surgery


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