STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System
Randall, Louise M.
Dietrich, Hans K.
Klover, Peter J.
Harris, Tajie H.
Beiting, Daniel P.
Koshy, Anita A.
Hunter, Christopher A.
AffiliationUniv Arizona, Dept Neurol, Dept Immunobiol, Inst BIO5
MetadataShow full item record
PublisherAMER SOC MICROBIOLOGY
CitationSTAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System 2016, 7 (6):e01881-16 mBio
RightsCopyright © 2016 Hidano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractThe local production of gamma interferon (IFN-gamma) 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-gamma 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.
VersionFinal published version
SponsorsCommonwealth of Pennsylvania; Fellowship from Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation; NIH [AI41158, 5R21EY021314, NS65116]; Deutsche Forschungsgemeinschaft; IRP of the NIDDK/NIH