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,suppresse s 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 highthroughput screen,identifying nine transcription factors that enhance stat1 function in the nucleus,including the orphan nuclear hormone receptor tlx. expression profiling reve aledthat 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 odulated in a context-specific manner by such “modifiers.”. © 2015 tierney et al.