The consequences of chitinase dependent cyst lysis in the CNS could potentially benefit either the host or the parasite. If the escaping bradyzoites were quickly killed by macrophages or associated immune cells, we would expect this mechanism to benefit the host and result in a lower parasite burden. Conversely, if bradyzoites are able to propagate and infect new cells, this could be a mechanism that promotes the persistence of the parasite in the brain. To investigate the role of AMCase in the brain in vivo, we infected WT and AMCase deficient mice and analyzed the immune response and parasite burden in the absence of chitinase activity. To determine if AMCase is required during the acute stage of infection, tissue samples from lungs were taken at day 7 and analyzed for parasite burden by qPCR. No significant differences in lung parasite load were found and serum cytokine concentrations were equivalent throughout acute infection ( Figure 6A-F) . Thus a lack of AMCase does not lead to deficient immune responses early on during infection in the periphery. At 5 weeks post infection, when systemic inflammation has been controlled and parasites are located solely in the brain predominantly as cysts containing bradyzoites [67, 70] parasite burden was evaluated. In the absence of AMCase, there was a significant increase (p = 0.0014) of approximately 2-fold in the total number but not the size of cysts in the brain (Figures 6G and 6H) . Differences in cyst burden were not observed at 3 weeks post infection ( Figure S6 ), a period representing the transition between acute and chronic infection, further suggesting that the increase in cyst burden is occurring due to events within the CNS during chronic infection. In addition, total parasite burden in the CNS as measured by qPCR was significantly greater by more than 2-fold (p = 0.0055) ( Figure 6I ) correlating with the appearance of more cysts histologically ( Figure 6J ). In addition, parasite burden was evaluated using RT-qPCR with stage-specific primers identifying tachyzoite (SAG1), bradyzoite (SAG4), and cyst (MAG1) specific transcripts [71] (Figure S6 ). Our results show similar increases in parasite burden for all three transcripts, suggesting that cyst lysis is also an important mechanism to control the cell invasive forms of the parasite. Flow cytometric analysis revealed no differences in infiltrating CD4+, CD8+ T cells, or macrophage populations ( Figure 6K) . Therefore, the increase in parasite burden is not due to a defect in infiltrating effector immune cells. Furthermore, AMCase2/2 mice failed to survive and succumbed to infection beginning at six weeks (p = 0.0177) ( Figure 6L ). Although some acute mortality was noted over several experiments significance was only achieved when chronic mortality was included. These results demonstrate that AMCase activity is required for the protective immune response to T. gondii during chronic infection in the brain and that AMCase mediated cyst lysis in the CNS is a beneficial mechanism for the host to control parasite burden at non-lethal levels.