Étude du rôle des exosomes et du DCIR dans les événements précoces de l'infection au virus de l'immunodéficience humaine

 

Caroline Gilbert

Centre de recherche du CHU de Québec

 

Domaine : maladies infectieuses et immunitaires

Programme chercheurs-boursiers - Junior 2

Concours 2015-2016

Recent studies showed that the earliest events involved in Human immunodeficiency virus type 1 (HIV-1) infection are major determinants of the subsequent pathological development of the disease.  Therefore, it is essential to understand these first events. Antigen-presenting cells such as dendritic cells internalize HIV-1 and then migrate to secondary lymphoid organs where the internalized virus is transferred to other cell types like CD4TL. These CD4TL then undergo a self-destructive process called apoptosis and release their viral load. We have shown that a receptor molecule called dendritic cell immunoreceptor or DCIR is involved in HIV-1 attachment to the immune cell membrane and in the transfer of the virus from dendritic cells to CD4TL and from apoptotic infected-CD4TL to normal CD4TL. We have also discovered that HIV-1-infected dendritic cells release sub-microscopic vesicles called exosomes. Exosomes play various intercellular communication roles and can be isolated from physiological fluids of HIV-1-infected patients. We were able to show that these released exosomes from HIV-infected dendritic cells contain molecules that promote apoptosis. Finally, we have determined that activation of DCIR is involved in exosome release by  dendritic cells.

Our research program comprises two premises, each having a fundamental and a clinical aspect. First, we propose to study how exosomes, containing particles that may infect immune cells, are able to deregulate the immune system, and how they can be used as biomarkers to monitor the progression of HIV-1 disease. Second, we are interested in studying the role of DCIR in the pathogenesis of HIV-1 infection and use this receptor for developing a therapeutic strategy based on blocking the binding of HIV-1 to DCIR. By studying the functions of exosomes and DCIR, we expect to be able to predict the early events in HIV-1 infection and develop new therapeutics to treat the disease.