Caractérisation de la base moléculaire de la tolérance aux maladies comme stratégie de défense de l'hôte contre les infections virales: communication inter-organelle orchestrée par les mitochondries pour limiter la gravité de la maladie virale

 

Ian Gaël Rodrigue-Gervais

Institut national de la recherche scientifique [INRS]

 

Domaine : maladies infectieuses et immunitaires

Programme Chercheurs-boursiers - Junior 1

Concours 2018-2019

Suicide of the infected cell is the supreme defense against viruses, which are obligate intracellular parasites. In this regard, the inflammasome is a multi-protein host defense machine that kills infected cells in an inflammatory death pathway driven by caspase-1. We study how infammasomes know when to trigger the signal telling a cell to die by pyroptosis. Surprisingly, extracellular inflammasomes continue to activate pyroptosis in an autonomous process when ingested by neighboring cells. Because of this, friendly fire is often an inescapable risk of this defense process and there must exist strict checks-and-balances between the ability to clear the virus and deterioration of our body's tissue functions through unwarranted cell loss. But few of the genes and pathways involved in control of tissue damage by the inflammasome are known.

Using methods that measure cellular behavior at a global level we are discovering how different metabolic signaling modules within the mitochondria and autophagy pathways interconnect to protect neighboring cell from engaging inflammasome-driven death. Our goal is to integrate these rulesets into dynamical models to understand, and eventually to manipulate, these checks of our cells to combat viral diseases like the flu that end up harming the body's own tissues even when the virus is wiped-out. This work also opens possibilities that this ruleset is conserved in many inflammasome-related diseases, including neurodegeneration.