title: ToxoplasmaEffectors Targeting Host Signaling and Transcription.
abstract: Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions. In parallel, studies on host-pathogen interactions identified many host signaling pathways that were mysteriously altered by infection. It was only with the advent of forward and reverse genetic strategies that the connections between individual parasite effectors and the specific host pathways that they targeted finally became clear. The current repertoire of parasite effectors includes ROP kinases and pseudokinases that are secreted during invasion and that block host immune pathways. Similarly, many secretory GRA proteins alter host gene expression by activating host transcription factors, through modification of chromatin, or by inducing small noncoding RNAs. These effectors highlight novel mechanisms by whichT. gondiihas learned to harness host signaling to favor intracellular survival and will guide future studies designed to uncover the additional complexity of this intricate host-pathogen interaction.
authors.affiliation: Institute for Advanced Biosciences, Team Host-Pathogen Interactions and Immunity to Infection, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.
authors.forename: Mohamed-Ali
authors.initials: MA
authors.lastname: Hakimi
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.|Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Olias
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA sibley@wustl.edu.
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
mesh_terms: D000818:Animals; D006790:Host-Parasite Interactions / Q000276:immunology / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction; D014122:Toxoplasma / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
keywords: chromatin remodeling; epigenetics; immune evasion; innate immunity; intracellular pathogen; serine/threonine kinases; signal transduction; transcription factors