Dendritic cells and immunoregulation in transplantation and immunopathology
Berthe-Marie Imbert
Research Scientist

Professor

Our projects concern the pathophysiology of viral infections in immunocompromised patients. We notably focus on persistant viruses which increase morbidity and mortality after solid organ or hematopoietic stem cell transplantations.  We mostly develop studies in clinical areas, and also some investigations to better understand the biological mechanisms involved in the infection progression and/or escape from immunity.

Description

Our investigations are part of the 3rd topic of team 1: “Immune responses to persistant viruses in transplanted patients (PIs BM Imbert-Marcille and C Bressollette)”

 

Due to the permanent development of new immunosuppressive therapies in transplantation, the patterns of opportunistic viral infections still evolve. The frequency of BK polyomavirus (BKPyV) and Human Herpesvirus 6 (HHV6) infections can vary according to the type of graft and the type of immunosuppressive therapy. These infections are causes of morbidity and in some cases transplant-related mortality. Therefore, it is of importance to characterize the immunovirological factors that contribute to these infections. The specific aims of this project are to study the Physiopathology of BKPyV and HHV-6 reactivations in the setting of new hematopoietic stem cell transplantation protocols. Over the last decade, umbilical cord blood (UCB) or more recently haploidentical stem cell transplantation have become well-established alternative sources of hematopoietic stem cells (HSC) in patients without available bone marrow or peripheral blood stem cell grafts. We recently demonstrated that UCB allogeneic stem cell transplantation is significantly associated with a higher risk of HHV-6 and BKPyV reactivations (Bressollette-Bodin et al, J Clin Virol, 2014; Illiaquer et al, J Infect Dis, 2014; Le Bourgeois et al, Exp Hematol, 2014). Our objective is to understand why the use of UCB is specifically associated with HHV-6 and BKPyV infections compared to other grafts and to other opportunistic viruses (hCMV, EBV, etc.). We postulated that this higher « susceptibility » originates from defects in the specific antiviral immune response and/or from an increase of permissive cells leading to infections of higher magnitude. This project rely on analysis of sequentially collected blood samples during the first months post-transplant and quantitation of viral DNA in different cell sub-types. This analysis will also include the study of the distribution and expression levels of the CD134 receptor for HHV-6. A prospective survey of viral infection occurrence will also be undertaken after haploidentical stem cell transplantation since immunosuppressive protocols and the increased number of HLA mismatches may favor the lack of immune control of opportunistic infections.