Understanding the time course of delta-9-tetrahydrocannabinol induced immunosuppression against C. albicans infection

The immunosuppressive effects of delta-9-tetrahydrocannabinol (???9-THC) are currently under investigation in numerous infectious disease models: bacterial, viral, and protozoan. However, less is known about the effect of cannabinoids on fungal infections. Our laboratory recently reported that ???9-THC suppresses mouse resistance to systemic C. albicans infection when the mice are challenged twice with the yeast with 0.75x105 C.albicans/mouse being administered on day 2, and 5x105 C.albicans/mouse on day 19. The mice were given ???9-THC (8mg/kg or 16mg/kg) on days 1-4, 8-11 and 15-18. The goal of this project is to determine whether the 12 day ???9-THC treatment is necessary to suppress mouse resistance to the yeast in this infection model. Our mice will be treated with ???9-THC (16mg/kg) on days 1-4 only and on days 15-18 only. Mouse resistance will be assessed by monitoring mouse survival (n=7 mice/group). In addition, mouse (n=5 mice/group) resistance will be assessed by quantifying tissue (brain, heart, kidneys, liver, and spleen) fungal load and cytokine levels