Cell Reports (Mar 2014)

miR-146a and miR-155 Delineate a MicroRNA Fingerprint Associated with Toxoplasma Persistence in the Host Brain

  • Dominique Cannella,
  • Marie-Pierre Brenier-Pinchart,
  • Laurence Braun,
  • Jason M. van Rooyen,
  • Alexandre Bougdour,
  • Olivier Bastien,
  • Michael S. Behnke,
  • Rose-Laurence Curt,
  • Aurélie Curt,
  • Jeroen P.J. Saeij,
  • L. David Sibley,
  • Hervé Pelloux,
  • Mohamed-Ali Hakimi

DOI
https://doi.org/10.1016/j.celrep.2014.02.002
Journal volume & issue
Vol. 6, no. 5
pp. 928 – 937

Abstract

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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.