The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii: e1002200
The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-[gamma])-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, identifyin...
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| Veröffentlicht in: | PLoS biology 2015-07, Vol.13 (7) |
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| creator | Beiting, Daniel P Hidano, Shinya Baggs, Julie E Geskes, Jeanne M Fang, Qun Wherry, E John Hunter, Christopher A Roos, David S Cherry, Sara |
| description | The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-[gamma])-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-[gamma] treatment TLX enhances the output of a subset of IFN-[gamma] 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." |
| doi_str_mv | 10.1371/journal.pbio.1002200 |
| format | Article |
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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-[gamma] treatment TLX enhances the output of a subset of IFN-[gamma] 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."</description><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.1002200</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Cytokines ; Cytomegalovirus ; Gene expression ; Infections ; Kinases ; Laboratory animals ; Ligands ; Parasites ; Proteins ; Toxoplasma gondii ; Transcription factors ; Tumor necrosis factor-TNF</subject><ispartof>PLoS biology, 2015-07, Vol.13 (7)</ispartof><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: . 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| subjects | Cytokines Cytomegalovirus Gene expression Infections Kinases Laboratory animals Ligands Parasites Proteins Toxoplasma gondii Transcription factors Tumor necrosis factor-TNF |
| title | The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii: e1002200 |
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