Epigenetic Reprogramming in Host-Parasite Coevolution: The Toxoplasma Paradigm

Abstract

Like many intracellular pathogens, the protozoan parasite Toxoplasma gondii has evolved sophisticated mechanisms to promote its transmission and persistence in a variety of hosts by injecting effector proteins that manipulate many processes in the cells it invades. Specifically, the parasite diverts host epigenetic modulators and modifiers from their native functions to rewire host gene expression to counteract the innate immune response and to limit its strength. The arms race between the parasite and its hosts has led to accelerated adaptive evolution of effector proteins and the unconventional secretion routes they use. This review provides an up-to-date overview of how T. gondii effectors, through the evolution of intrinsically disordered domains, the formation of supramolecular complexes, and the use of molecular mimicry, target host transcription factors that act as coordinating nodes, as well as chromatin-modifying enzymes, to control the fate of infected cells and ultimately the outcome of infection.

Keywords: Toxoplasma gondii; epigenetics; innate immunity; secreted effectors; transcription.