miR-146a and miR-155 delineate a MicroRNA fingerprint associated with Toxoplasma persistence in the host brain

Cell Rep. 2014 Mar 13;6(5):928-37. doi: 10.1016/j.celrep.2014.02.002. Epub 2014 Feb 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / parasitology*
  • Cell Fractionation
  • Female
  • Fibroblasts / parasitology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Signal Transduction
  • Tissue Array Analysis
  • Toxoplasma / physiology*
  • Toxoplasmosis / genetics*
  • Transfection

Substances

  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Mirn155 microRNA, mouse