ChronicToxoplasma gondiiinfection curtails the cytotoxic potential of acute T cell responses to West Nile virus in the brain

Abstract

ABSTRACTToxoplasma gondii (T. gondii), a common brain-tropic parasite, chronically infects the central nervous system (CNS) of up to a third of the world’s population. Constant immune surveillance interrupts cyst reactivation within the CNS and dramatically alters the immune landscape of the brain. West Nile virus (WNV) is a mosquito-borne infection with a clinical spectrum ranging from asymptomatic to mild flu-like symptoms to severe neuroinvasive disease. In a cohort of WNV infected people, we discovered a positive correlation between WNV disease severity andT. gondiiseropositivity. In a mouse model pairing chronicT. gondiiwith acute WNV infection, we found an increased susceptibility of mice to WNV, with reduced granzyme B expression in WNV-specific T cells and increased regulatory T cell (Treg) numbers in the brain, but not the periphery. This demonstrates that theT. gondii-infected tissue microenvironment impairs immune defense against other brain infections by blunting local T cell responses.