title: miR-146a and miR-155 delineate a MicroRNA fingerprint associated with Toxoplasma persistence in the host brain.
abstract: microRNAs were recently found to be regulators of the host response to infection by apicomplexan parasites. In this study, we identified two immunomodulatory microRNAs, miR-146a and miR-155, that were coinduced in the brains of mice challenged with Toxoplasma in a strain-specific manner. These microRNAs define a characteristic fingerprint for infection by type II strains, which are the most prevalent cause of human toxoplasmosis in Europe and North America. Using forward genetics, we showed that strain-specific differences in miR-146a modulation were in part mediated by the rhoptry kinase, ROP16. Remarkably, we found that miR-146a deficiency led to better control of parasite burden in the gut and most likely of early parasite dissemination in the brain tissue, resulting in the long-term survival of mice.
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Cannella
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Brenier-Pinchart
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Braun
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France; European Molecular Biology Laboratory, 38042 Grenoble, France.
authors.forename: Jason M
authors.initials: JM
authors.lastname: van Rooyen
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bougdour
authors.affiliation: UMR 5168, CNRS/INRA, Université Joseph Fourier, CEA, 38054 Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bastien
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Behnke
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Rose-Laurence
authors.initials: RL
authors.lastname: Curt
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Curt
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jeroen P J
authors.initials: JP
authors.lastname: Saeij
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Pelloux
authors.affiliation: CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France. Electronic address: mohamed-ali.hakimi@ujf-grenoble.fr.
authors.forename: Mohamed-Ali
authors.initials: MA
authors.lastname: Hakimi
mesh_terms: D000818:Animals; D001921:Brain / Q000469:parasitology*; D002458:Cell Fractionation; D005260:Female; D005347:Fibroblasts / Q000469:parasitology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction; D046888:Tissue Array Analysis; D014122:Toxoplasma / Q000502:physiology*; D014123:Toxoplasmosis / Q000235:genetics*; D014162:Transfection
chemical_list: D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; C532623:Mirn155 microRNA, mouse