serum response factor regulates immediate early host gene expression in toxoplasma gondii-infected host cells血清响应因子调节立即早期基因表达宿主弓形虫gondii-infected宿主细胞.pdfVIP

Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells 1. 1. 1¤ 2 1 Mandi Wiley , Crystal Teygong , Eric Phelps , Jay Radke , Ira J. Blader * 1 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 2 Department of Veterinary Molecular Biology the Center for Immunotherapies to Zoonotic Diseases, Montana State University, Bozeman, Montana, United States of America 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 canin