title: Serum response factor regulates immediate early host gene expression in Toxoplasma gondii-infected host cells.
abstract: Toxoplasma gondii is a wide spread pathogen that can cause severe and even fatal disease in fetuses and immune-compromised hosts. As an obligate intracellular parasite, Toxoplasma must alter the environment of its host cell in order to establish its replicative niche. This is accomplished, in part, by secretion of factors into the host cell that act to modulate processes such as transcription. Previous studies demonstrated that genes encoding transcription factors such as c-jun, junB, EGR1, and EGR2 were amongst the host genes that were the most rapidly upregulated following infection. In cells stimulated with growth factors, these genes are regulated by a transcription factor named Serum Response Factor. Serum Response Factor is a ubiquitously expressed DNA binding protein that regulates growth and actin cytoskeleton genes via MAP kinase or actin cytoskeletal signaling, respectively. Here, we report that Toxoplasma infection leads to the rapid activation of Serum Response Factor. Serum Response Factor activation is a Toxoplasma-specific event since the transcription factor is not activated by the closely related protozoan parasite, Neospora caninum. We further demonstrate that Serum Response Factor activation requires a parasite-derived secreted factor that signals via host MAP kinases but independently of the host actin cytoskeleton. Together, these data define Serum Response Factor as a host cell transcription factor that regulates immediate early gene expression in Toxoplasma-infected cells.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Mandi
authors.initials: M
authors.lastname: Wiley
authors.forename: Crystal
authors.initials: C
authors.lastname: Teygong
authors.forename: Eric
authors.initials: E
authors.lastname: Phelps
authors.forename: Jay
authors.initials: J
authors.lastname: Radke
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Blader
mesh_terms: D000818:Animals; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D051767:Early Growth Response Protein 2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D010271:Parasites / Q000502:physiology; D015800:Protozoan Proteins / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051820:TCF Transcription Factors / Q000378:metabolism; D014122:Toxoplasma / Q000502:physiology*; D014123:Toxoplasmosis / Q000235:genetics / Q000469:parasitology*
chemical_list: C497325:EGR1 protein, human; C497326:EGR2 protein, human; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D015800:Protozoan Proteins; D026362:Serum Response Factor; D051820:TCF Transcription Factors