STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System
ABSTRACT 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...
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American Society for Microbiology
2016
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oai:doaj.org-article:b1805e78fdca4cabb73b13758748f7152021-11-15T15:50:16ZSTAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System10.1128/mBio.01881-162150-7511https://doaj.org/article/b1805e78fdca4cabb73b13758748f7152016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01881-16https://doaj.org/toc/2150-7511ABSTRACT 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.Shinya HidanoLouise M. RandallLucas DawsonHans K. DietrichChristoph KonradtPeter J. KloverBeena JohnTajie H. HarrisQun FangBradley TurekTakashi KobayashiLothar HennighausenDaniel P. BeitingAnita A. KoshyChristopher A. HunterAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016) |
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Microbiology QR1-502 |
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Microbiology QR1-502 Shinya Hidano Louise M. Randall Lucas Dawson Hans K. Dietrich Christoph Konradt Peter J. Klover Beena John Tajie H. Harris Qun Fang Bradley Turek Takashi Kobayashi Lothar Hennighausen Daniel P. Beiting Anita A. Koshy Christopher A. Hunter STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System |
| description |
ABSTRACT 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. |
| format |
article |
| author |
Shinya Hidano Louise M. Randall Lucas Dawson Hans K. Dietrich Christoph Konradt Peter J. Klover Beena John Tajie H. Harris Qun Fang Bradley Turek Takashi Kobayashi Lothar Hennighausen Daniel P. Beiting Anita A. Koshy Christopher A. Hunter |
| author_facet |
Shinya Hidano Louise M. Randall Lucas Dawson Hans K. Dietrich Christoph Konradt Peter J. Klover Beena John Tajie H. Harris Qun Fang Bradley Turek Takashi Kobayashi Lothar Hennighausen Daniel P. Beiting Anita A. Koshy Christopher A. Hunter |
| author_sort |
Shinya Hidano |
| title |
STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System |
| title_short |
STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System |
| title_full |
STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System |
| title_fullStr |
STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System |
| title_full_unstemmed |
STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System |
| title_sort |
stat1 signaling in astrocytes is essential for control of infection in the central nervous system |
| publisher |
American Society for Microbiology |
| publishDate |
2016 |
| url |
https://doaj.org/article/b1805e78fdca4cabb73b13758748f715 |
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