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The clever strategies used by intracellular parasites to hijack host gene expression

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Abstract

Intracellular pathogens need to develop sophisticated mechanisms to survive and thrive in the hostile environment within host cells. Unicellular, eukaryotic parasites from the Apicomplexa phylum have become masters of manipulating their host cells, exploiting signaling, and metabolic pathways to hijack host gene expression to their own advantage. These intracellular parasites have developed a wide range of strategies that affect transcriptional machineries and epigenetic events in the host cell nucleus. In recent years, many laboratories have risen to the challenge of studying the epigenetics of host-pathogen interactions with the hope that unraveling the complexity of the mechanisms involved will provide important insights into parasitism and provide clues to fight infection. In this review, we survey some of these many strategies that Apicomplexan parasites employ to hijack their hosts, including inducing epigenetic enzymes, secreting epigenators into host cells, sequestering host signaling proteins, and co-opting non-coding RNAs to change gene and protein expression. We cite selected examples from the literature on Apicomplexa parasites (including Toxoplasma, Theileria, and Cryptosporidium) to highlight the success of these parasitic processes. We marvel at the effectiveness of the strategies that these pathogens have evolved and wonder what mysteries lie ahead in exploring the epigenetics of host–parasite interactions.

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Acknowledgments

JBW is a senior member of the Institut Universitaire de France (IUF). We thanks members of the Weitzman lab and members of the UMR7216 for helpful discussions.

Funding

The work in our lab is supported by the LabEx “Who Am I?” #ANR-11-LABX-0071, and the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its “Investments for the Future” program, the Agence Nationale de la Recherche (ANR PATHO-METHYLOME #ANR-15-CE12-0020), and the Plan Cancer “Epigénétique et cancer” 2015 (PARA-CAN #PARA-15-RCA).

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  1. UMR 7216 Epigenetics and Cell Fate, CNRS, Université de Paris, Bâtiment Lamarck, Case 7042, 35 rue Hélène Brion, 75205, Paris cedex 13, France

    Marie Villares, Jérémy Berthelet & Jonathan B. Weitzman

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  1. Marie Villares
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  2. Jérémy Berthelet
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  3. Jonathan B. Weitzman
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Correspondence to Jonathan B. Weitzman.

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This article is a contribution to the special issue on Infection-induced epigenetic changes and the pathogenesis of diseases - Guest Editor: Nicole Fischer

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Villares, M., Berthelet, J. & Weitzman, J.B. The clever strategies used by intracellular parasites to hijack host gene expression. Semin Immunopathol 42, 215–226 (2020). https://doi.org/10.1007/s00281-020-00779-z

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