The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii.
The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-γ)-induced signal transducer and activator of transcription 1 (STAT1) activity. We exploited this well-defined host-pathogen interaction as the basis for a high-throughput screen, identifying nine...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-07-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.1002200 |
| _version_ | 1819021621428486144 |
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| author | Daniel P Beiting Shinya Hidano Julie E Baggs Jeanne M Geskes Qun Fang E John Wherry Christopher A Hunter David S Roos Sara Cherry |
| author_facet | Daniel P Beiting Shinya Hidano Julie E Baggs Jeanne M Geskes Qun Fang E John Wherry Christopher A Hunter David S Roos Sara Cherry |
| author_sort | Daniel P Beiting |
| collection | DOAJ |
| description | The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-γ)-induced signal transducer and activator of transcription 1 (STAT1) activity. We exploited this well-defined host-pathogen interaction as the basis for a high-throughput screen, identifying nine transcription factors that enhance STAT1 function in the nucleus, including the orphan nuclear hormone receptor TLX. Expression profiling revealed that upon IFN-γ treatment TLX enhances the output of a subset of IFN-γ target genes, which we found is dependent on TLX binding at those loci. Moreover, infection of TLX deficient mice with the intracellular parasite Toxoplasma results in impaired production of the STAT1-dependent cytokine interleukin-12 by dendritic cells and increased parasite burden in the brain during chronic infection. These results demonstrate a previously unrecognized role for this orphan nuclear hormone receptor in regulating STAT1 signaling and host defense and reveal that STAT1 activity can be modulated in a context-specific manner by such "modifiers." |
| first_indexed | 2024-12-21T04:10:01Z |
| format | Article |
| id | doaj.art-58f2cfedb6824570a21d6c85c0d5c279 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-21T04:10:01Z |
| publishDate | 2015-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-58f2cfedb6824570a21d6c85c0d5c2792022-12-21T19:16:29ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852015-07-01137e100220010.1371/journal.pbio.1002200The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii.Daniel P BeitingShinya HidanoJulie E BaggsJeanne M GeskesQun FangE John WherryChristopher A HunterDavid S RoosSara CherryThe protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-γ)-induced signal transducer and activator of transcription 1 (STAT1) activity. We exploited this well-defined host-pathogen interaction as the basis for a high-throughput screen, identifying nine transcription factors that enhance STAT1 function in the nucleus, including the orphan nuclear hormone receptor TLX. Expression profiling revealed that upon IFN-γ treatment TLX enhances the output of a subset of IFN-γ target genes, which we found is dependent on TLX binding at those loci. Moreover, infection of TLX deficient mice with the intracellular parasite Toxoplasma results in impaired production of the STAT1-dependent cytokine interleukin-12 by dendritic cells and increased parasite burden in the brain during chronic infection. These results demonstrate a previously unrecognized role for this orphan nuclear hormone receptor in regulating STAT1 signaling and host defense and reveal that STAT1 activity can be modulated in a context-specific manner by such "modifiers."https://doi.org/10.1371/journal.pbio.1002200 |
| spellingShingle | Daniel P Beiting Shinya Hidano Julie E Baggs Jeanne M Geskes Qun Fang E John Wherry Christopher A Hunter David S Roos Sara Cherry The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii. PLoS Biology |
| title | The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii. |
| title_full | The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii. |
| title_fullStr | The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii. |
| title_full_unstemmed | The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii. |
| title_short | The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii. |
| title_sort | orphan nuclear receptor tlx is an enhancer of stat1 mediated transcription and immunity to toxoplasma gondii |
| url | https://doi.org/10.1371/journal.pbio.1002200 |
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