The protozoan parasite Toxoplasma gondii infects a broad range of hosts, with a seroprevalence in man of about 30 per cent. It is unclear how Toxoplasma maintains the intricate balance between survival and host defense.
IFNγ, the main cytokine responsible for its control, activates cells to restrict intracellular parasite replication or to kill intracellular Toxoplasma. Cell-mediated immunity, driven mostly by CD8 T cells, confers resistance to the chronic phase of the parasite. The outcome of an infection with Toxoplasma is determined not only by the host's immune status, but also by the genotype of the infecting strain.
The major cause of Toxoplasma pathogenesis results from parasite burden, concurrent with an over-stimulation of the immune system in the form of high levels of T helper cell type 1 cytokines, increased apoptosis and organ damage.
Our long-term goal is to identify novel pathways and mechanisms of host resistance to Toxoplasma. We are studying how the parasitophorous vacuole (PV) is remodeled within host cells to limit parasite replication and/or induce immune defence mechanisms. We are interested in defining what shapes the functionality of CD8 T cells that control chronic Toxoplasmainfection.