miR-146a and miR-155 delineate a MicroRNA fingerprint associated with Toxoplasma persistence in the host brain
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Updated: May 2, 2026
3-D Imaging and Analysis of Neurons Infected In Vivo with Toxoplasma gondii
Published on: December 9, 2014
Dominique Cannella1, Marie-Pierre Brenier-Pinchart1, Laurence Braun1
1CNRS, UMR5163, LAPM, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
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.
Insights
Two microRNAs, miR-146a and miR-155, are key regulators in the host response to Toxoplasma infection. Their levels indicate infection strain, and miR-146a deficiency improves mouse survival.
Area of Science:
- Immunology
- Molecular Biology
- Parasitology
Background:
- MicroRNAs (miRNAs) are recognized regulators of host responses to parasitic infections.
- Apicomplexan parasites, such as Toxoplasma gondii, pose significant health challenges globally.
Purpose of the Study:
- To identify specific microRNAs involved in the host response to Toxoplasma infection.
- To investigate the role of these microRNAs in strain-specific infection dynamics and host survival.
Main Methods:
- Co-expression analysis of microRNAs in infected mouse brains.
- Forward genetics to identify genetic mediators of microRNA regulation.
- Assessment of parasite burden and host survival in genetically modified mice.
Main Results:
- Two immunomodulatory microRNAs, miR-146a and miR-155, were co-induced in mouse brains during Toxoplasma infection.
- These microRNAs serve as a molecular signature for type II Toxoplasma strains, prevalent in human infections.
- The rhoptry kinase ROP16 partially mediates strain-specific miR-146a modulation.
- miR-146a deficiency enhanced control of parasite burden and improved long-term survival in mice.
Conclusions:
- miR-146a and miR-155 are critical regulators of the host immune response to Toxoplasma.
- Strain-specific modulation of miR-146a by parasite factors like ROP16 influences infection outcome.
- Targeting miR-146a represents a potential therapeutic strategy for toxoplasmosis.
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