Epigenetics: A New Model for Intracellular Parasite–Host Cell Regulation

Intracellular protozoan parasites are an extremely important class of pathogens that cause a spectrum of diseases in human and animal hosts. There is a growing body of evidence suggesting that protozoan parasites, like other prokaryotic and viral pathogens, manipulate host cells via epigenetic modifications of the host genome that alter transcription and corresponding signaling pathways. In light of these data, we examine the role of epigenetics in downregulation of host macrophages by Leishmania that could potentially lead to a permanent state of inactivation, thus favoring pathogen survival and disease progression.

TrendsEpigenetic regulation of gene expression is essential for development and differentiation in many systems.There is a growing body of evidence suggesting that protozoan parasites such as Leishmania, Toxoplasma, and Theileria manipulate host cells via epigenetic modification of host gene expression.A hallmark of Leishmania infection is parasite-induced downregulation and inhibition of the activation of macrophage innate immunity enabling parasite survival and replication.Based on recent data, a new hypothesis is proposed where intracellular infection of macrophages by Leishmania induces epigenetic modifications at the level of DNA methylation of the host cell genome, resulting in permanent downregulation and inhibition of host defense mechanisms to promote the intracellular replication and survival of the pathogen.