STAT1 signaling in astrocytes is essential for control of infection in the central nervous system

The local production of IFN-γ is important to control Toxoplasma gondii in the brain but the basis for these protective effects are not fully understood. The studies presented here reveal that the ability of IFN-γ to inhibit parasite replication in astrocytes in vitro is dependent on signal transducer and activator of transcription 1 (STAT1) and that mice that specifically lack STAT1 in astrocytes are unable to limit parasite replication in the central nervous system (CNS). This susceptibility is associated with a loss of anti-microbial pathways but also altered local immune responses that include decreased T cell production of IFN-γ and elevated expression of inhibitory receptors. These results identify a critical role for astrocytes in limiting the replication of an important opportunistic pathogen and highlight their role in coordinating local anti-parasitic responses. Three conditions were analyzed. Primary mouse astrocytes derived from mixed glial cultures from the cerebral cortex of 1-3 day old neonatal mice were either left untreated, or were stimulated with 10ng/ml of recombinant mouse IFNg or IFNa for 12 hours. Two biological replicates were used for each condition.