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Cell Rep ; 6(5): 928-37, 2014 Mar 13.
Article in English | MEDLINE | ID: mdl-24582962

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.


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