4.8 Article

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

期刊

CELL REPORTS
卷 6, 期 5, 页码 928-937

出版社

CELL PRESS
DOI: 10.1016/j.celrep.2014.02.002

关键词

-

资金

  1. ANR Blanc grant APImiR [ANR 2010 BLAN 1315 01]
  2. ANR blanc ToxoHDAC [ANR-12-BSV3-0009-01]
  3. LabEx ParaFrap [ANR-11-LABX-0024]
  4. National Institutes of Health [R01-AI080621]
  5. Agence Nationale de la Recherche (ANR) [ANR-12-BSV3-0009] Funding Source: Agence Nationale de la Recherche (ANR)

向作者/读者索取更多资源

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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Review Parasitology

The developmental trajectories of Toxoplasma stem from an elaborate epigenetic rewiring

Dayana C. Farhat, Mohamed-Ali Hakimi

Summary: Toxoplasma gondii is considered a successful parasitic pathogen due to its flexibility in responding to different environments, relying on coordinated developmental abilities. Recent studies have uncovered how master regulators epigenetically regulate its development, highlighting new opportunities for epigenetic reprogramming in the field.

TRENDS IN PARASITOLOGY (2022)

Article Microbiology

The Toxoplasma Polymorphic Effector GRA15 Mediates Seizure Induction by Modulating Interleukin-1 Signaling in the Brain

Taylor G. Glausen, Gabriela L. Carrillo, Richard M. Jin, Jon P. Boyle, Jeroen P. J. Saeij, Elizabeth A. Wohlfert, Michael A. Fox, Ira J. Blader

Summary: Toxoplasmic encephalitis can induce seizures in infected individuals, and the parasite gene GRA15 plays a key role in this process by increasing host IL-1 receptor signaling. Inhibition of IL-1 signaling reduces seizure severity in Toxoplasma-infected mice, revealing a potential therapeutic target for controlling seizures associated with toxoplasmic encephalitis.
Review Microbiology

Epigenetic Reprogramming in Host-Parasite Coevolution: The Toxoplasma Paradigm

Mohamed-Ali Hakimi

Summary: Like many intracellular pathogens, Toxoplasma gondii uses effector proteins to manipulate host cells and promote transmission and persistence. This review summarizes how T. gondii effectors control the fate of infected cells and the outcome of infection through specific mechanisms.

ANNUAL REVIEW OF MICROBIOLOGY (2022)

Editorial Material Microbiology

Hunger games in the host cell: Toxoplasma traps and skins host mitochondria

Mohamed-Ali Hakimi

Summary: Toxoplasma gondii weakens host metabolic defenses by trapping mitochondrial proteins.

CELL HOST & MICROBE (2022)

Article Pathology

Multicenter Evaluation of the Toxoplasma RealCycler Universal PCR Assay on 168 Characterized Human Samples

Marie-Pierre Brenier-Pinchart, Denis Filisetti, Sophie Cassaing, Emmanuelle Varlet-Marie, Florence Robert-Gangneux, Laurence Delhaes, Juliette Guitard, Helene Yera, Patrick Bastien, Herve Pelloux, Yvon Sterkers

Summary: This multicenter study assessed the performance of the Toxoplasma RealCycler Universal assay for the diagnosis of toxoplasmosis. The commercial PCR showed high sensitivity and specificity in detecting low parasitic loads, making it suitable for diagnosing different forms of toxoplasmosis.

JOURNAL OF MOLECULAR DIAGNOSTICS (2022)

Article Microbiology

Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development

Yogavel Manickam, Nipun Malhotra, Siddhartha Mishra, Palak Babbar, Abhishek Dusane, Benoit Laleu, Valeria Bellini, Mohamed-Ali Hakimi, Alexandre Bougdour, Amit Sharma

Summary: This study describes the simultaneous targeting of multiple binding sites of the enzyme prolyl-tRNA synthetase (PRS) in Toxoplasma gondii using two potent inhibitors, halofuginone (HFG) and L95. The inhibitors form a ternary complex with the enzyme, inhibiting its activity and showing additive effects in parasite inhibition assays. This novel approach validates the potential of targeting multiple pockets to inhibit druggable proteins, providing a structural framework for further drug development.

PLOS PATHOGENS (2022)

Article Cell Biology

Altiratinib blocks Toxoplasma gondii and Plasmodium falciparum development by selectively targeting a spliceosome kinase

Christopher Swale, Valeria Bellini, Matthew W. Bowler, Nardella Flore, Marie-Pierre Brenier-Pinchart, Dominique Cannella, Lucid Belmudes, Caroline Mas, Yohann Coute, Fabrice Laurent, Artur Scherf, Alexandre Bougdour, Mohamed-Ali Hakimi

Summary: The Apicomplexa, a phylum of single-celled protozoa, cause severe parasitic diseases in humans and animals. Current therapeutics are limited by their efficacy and resistance. In this study, altiratinib, originally developed for glioblastoma, is identified as a potential drug candidate with broad spectrum activity against apicomplexans. Altiratinib specifically targets the TgPRP4K of T. gondii and inhibits the development of intracellular parasites. The molecular basis of the inhibitory mechanism and species selectivity is further elucidated.

SCIENCE TRANSLATIONAL MEDICINE (2022)

Article Microbiology

The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages

Arne L. Ten Hoeve, Laurence Braun, Matias E. Rodriguez, Gabriela C. Olivera, Alexandre Bougdour, Lucid Belmudes, Yohann Coute, Jeroen P. J. Saeij, Mohamed-Ali Hakimi, Antonio Barragan

Summary: This study reveals how the intracellular parasite Toxoplasma gondii exploits the chemotactic migration ability of macrophages, highlighting the migratory plasticity of differentiated cells in the mononuclear phagocyte system. The parasite effector GRA28 cooperates with host chromatin remodelers to drive the migration of parasitized macrophages. These findings provide insights into the mechanisms underlying the dissemination of T. gondii and the interaction between the parasite and host cells.

CELL HOST & MICROBE (2022)

Article Microbiology

Late Embryogenesis Abundant Proteins Contribute to the Resistance of Toxoplasma gondii Oocysts against Environmental Stresses

David Arranz-Solis, David Warschkau, Benedikt T. Fabian, Frank Seeber, Jeroen P. J. Saeij

Summary: Toxoplasma gondii oocysts, shed in feces from infected felines, are highly infectious and can survive in the environment for years. The oocysts have a stable and highly infectious nature, but their ability to resist environmental stressors is not fully understood.
Article Microbiology

Targeting prolyl-tRNA synthetase via a series of ATP-mimetics to accelerate drug discovery against toxoplasmosis

Manickam Yogavel, Alexandre Bougdour, Siddhartha Mishra, Nipun Malhotra, Jyoti Chhibber-Goel, Valeria J. Bellini, Karl Harlos, Benoit J. Laleu, Mohamed-Ali Hakimi, Amit J. Sharma

Summary: Researchers have discovered that a compound called PPL can bind to a protein involved in the pathogenic mechanism of the Toxoplasma parasite and kill it. Mutations in the protein structure related to PPL have been identified through genetic mutation and DNA sequencing analysis. Therefore, this study provides a method for enhancing the activity of this compound series.

PLOS PATHOGENS (2023)

Review Cell Biology

3'-end mRNA processing within apicomplexan parasites, a patchwork of classic, and unexpected players

Christopher Swale, Mohamed-Ali Hakimi

Summary: The 3'-end processing of mRNA is a co-transcriptional process that involves a complex composed of cleavage and polyadenylation specificity factors (CPSFs) to recognize cis-sequence elements on nascent mRNA and carry out cleavage and polyadenylation reactions. Recent studies have provided a mechanistic understanding of this machinery in yeast or metazoans, and the discovery of small molecule inhibitors of CPSF function has stimulated interest in studying this machinery in Apicomplexa. The CPSF complex integrates a novel reader of the N6-methyladenosine (m6A) in these organisms and bridges m6A metabolism to transcription termination.

WILEY INTERDISCIPLINARY REVIEWS-RNA (2023)

暂无数据