Abstract
Abstract Toxoplasma gondii is a neurotropic parasite with high mortality rates in immunocompromised individuals. Successful therapies have been developed against the acute tachyzoite stage, but no treatment options exist to target the latent form of the parasite – bradyzoites that form cysts within neurons. It is thought that residence of cysts in neurons shelters T. gondii from immune recognition and clearance. However, a decline in cyst numbers over time suggests the presence of anti-cyst immunity. Additionally, neuronal deletion of STAT1 results in increased cyst size and number, but no change in tachyzoite replication, providing evidence for IFN-γ-mediated cyst control. T cells are a major source of IFN-γ and are crucial for parasite control in the CNS, but it remains unclear if T cells directly target cyst-infected neurons. The use of transgenic parasites with bradyzoite-restricted OVA expression (BagOVA) reveals that cyst-derived antigen can induce OT-I CD8+ T cell responses in the brains of chronically infected mice. These cyst-specific OT-Is have distinct effector phenotypes and cytokine production when compared to T cells responding to antigen expressed by both tachyzoites and bradyzoites (ptubOVA). To determine whether neurons directly present cyst antigen to induce CD8+ T cell responses in BagOVA infection, mice with neuronal-specific loss of MHCI were generated. Infection of these mice showed no significant change in the magnitude of T cell responses or parasite burden in the CNS. Together these findings reveal that T cell responses can be mounted against cyst antigens, but another cell type likely mediates cross presentation of cyst derived antigens. Supported by grants from NIH (R01 580-5803-4-580697-XXXX-2000-3000)
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