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

• Main Authors: Cannella, Dominique (Author), Brenier-Pinchart (Author), Braun, Laurence (Author), van Rooyen, Jason M (Author), Bougdour, Alexandre (Author), Bastien, Olivier (Author), Behnke, Michael S (Author), Curt, Rose-Laurence (Author), Sibley, L. David (Author), Hakimi, Mohamed-Ali (Author), Saeij, Jeroen (Contributor), Curt, Aurelie (Author), Pelloux, Herve (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2015-04-23T19:52:56Z.
• Subjects: Article
• Online Access: Get fulltext

 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.