Research Group

  • Dr Franck Halary, Principal Investigator
  • Mr Jérémy Reignier, Co-Investigator
  • Dr Iulia Mocan, Co-Investigator
  • Prof. Jean-François Moreau, Research Associate
  • Prof. Pierre Merville, Research Associate

Location

  • Université de Nantes, Nantes, France

Title

  • Study of Cytomegalovirus/dendritic Cells Interplays in Kidney Transplantation

Immunosuppressive drugs have been extensively used for several decades in human solid organ transplantation leading to a strong decrease of acute graft rejection. By weakening the immune response in transplant recipients, opportunistic pathogens such as cytomegalovirus (CMV) arise and may be responsible for chronic rejection of the grafted organ. Since CMV infection or reactivation often occurs after organ transplantation, patients are now given prophylactic anti-viral drugs. However, several recent studies reported that these therapies, beside their significant side-effects, did not definitely eliminate the virus but only delayed CMV infection appearance. Two major drawbacks have been recently listed as consequences of anti-viral prophylactic treatments: firstly, long-term anti-viral treatments may give rise to resistant CMV strains and, secondly, since anti-CMV drugs target only replicating virus, cell-protected or resistant virions may escape antiviral drugs. This may lead to the usually observed infection relapse when prophylaxis is stopped. We recently reported that dendritic cells (DC) were able to internalize CMV particles. These virions kept their infectious potential for a much longer time than cell-free virions. DC were not only able to protect CMV particle into as yet uncharacterized endocytic vesicles, but were also rendered permissive to CMV infection when harboring particular well-defined lectins. This previous work suggested that in vivo DC could likely capture CMV via several specific receptors at sites of inoculation or reactivation and protect it from extracellular neutralization by a rapid internalization. Our present research project has been designed to document (i) how the CMV may use DC to escape from a rapid immune inactivation, (ii) how the commonly used immunosuppressive and antiviral drugs may favor or inhibit the CMV protection by DC, (iii) how DC may sense and capture CMV at sites of inoculation in a three-dimensional experimental model of human mucosa and finally, (iv) to screen new anti-viral molecules that may also target non-replicating CMV. In summary, this project will help us to shed light on as yet unknown roles of DC toward CMV in the field of kidney transplantation.

Progress Report
Final Report