MBio. 2016 Nov 8;7(6). pii: e01881-16. doi: 10.1128/mBio.01881-16.
Hidano S1,2,
Randall LM3,
Dawson L1,
Dietrich HK4,
Konradt C1,
Klover PJ5,
John B1,
Harris TH6,
Fang Q1,
Turek B1,
Kobayashi T2,
Hennighausen L5,
Beiting DP1,
Koshy AA4,
Hunter CA7.
The local production of gamma interferon (IFN-γ) is important to control Toxoplasma gondii in the brain, but the basis for these protective effects is 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 antimicrobial pathways and increased cyst formation in astrocytes. These results identify a critical role for astrocytes in limiting the replication of an important opportunistic pathogen.
IMPORTANCE:
Astrocytes are the most numerous cell type in the brain, and they are activated in response to many types of neuroinflammation, but their function in the control of CNS-specific infection is unclear. The parasite Toxoplasma gondii is one of the few clinically relevant microorganisms that naturally infects astrocytes, and the studies presented here establish that the ability of astrocytes to inhibit parasite replication is essential for the local control of this opportunistic pathogen. Together, these studies establish a key role for astrocytes as effector cells and in the coordination of many aspects of the protective immune response that operates in the brain.
Copyright © 2016 Hidano et al.
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