International Journal of Molecular Sciences Review Host Epigenetics in Intracellular Pathogen Infections Marek Fol *, Marcin Włodarczyk and Magdalena Druszczy ´nska Division of Cellular Immunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland; [email protected] (M.W.); [email protected] (M.D.) * Correspondence: [email protected]; Tel.: +48-42-635-44-72 Received: 27 May 2020; Accepted: 26 June 2020; Published: 27 June 2020 Abstract: Some intracellular pathogens are able to avoid the defense mechanisms contributing to host epigenetic modifications. These changes trigger alterations tothe chromatin structure and on the transcriptional level of genes involved in the pathogenesis of many bacterial diseases. In this way, pathogens manipulate the host cell for their own survival. The better understanding of epigenetic consequences in bacterial infection may open the door for designing new vaccine approaches and therapeutic implications. This article characterizes selected intracellular bacterial pathogens, including Mycobacterium spp., Listeria spp., Chlamydia spp., Mycoplasma spp., Rickettsia spp., Legionella spp. and Yersinia spp., which can modulate and reprogram of defense genes in host innate immune cells. Keywords: epigenetic modifications; intracellular pathogens; immune cells 1. Introduction Epigenetic regulation of the gene activity is a subject of deep and still-increasing interest. The appearance of an epigenetic trait defined as “a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence” can be triggered by changes in the environment of the cell, precisely described and discussed by Berger et al. [1]. There is some evidence suggesting that certain microbial agents, e.g., Helicobacter pylori [2], Porphyromonas gingivalis, Fusobacterium nucleatum [3], Streptococcus bovis, Chlamydia pneumoniae, Campylobacter rectus, Epstein–Barr virus, hepatitis viruses, human papilloma virus, polyoma viruses, can contribute to the host epigenetic changes and are frequently associated with carcinogenesis [4]. In the context of host–pathogen interactions, microorganism trying to conquer the host would be regarded as co-called “epigenetor” (term proposed by Berger et al. [1])—a factor which descends from environment and triggers a cascade of events ultimately leading to the modulation of the host epigenome. The most common mechanisms by which epigenetics control changes in gene expression involve histone acetylation, histone deacetylation, histone methylation and DNA methylation [5–7]. However, these epigenetic modifications induced by the infectious agents in host cells are still not sufficiently explored. Possibly, these infectious agents have developed a wide variety of epigenetic regulatory mechanisms, through which they are able to effectively exploit the epigenome of the host for their own benefits (Figure1)[ 8]. In this review, the main interest is focused on certain intracellular bacterial pathogens: Mycobacterium tuberculosis—an obligatory, aerobic bacillus still remaining one of the major global health problems since it is estimated that one fourth of global human population is infected with that pathogen [9,10] and Listeria monocytogenes—mainly transmitted through the consumption of contaminated food, causing listeriosis, a disease whose importance is not sufficiently recognized [11]. We have also compiled selected information regarding another four obligatory or facultative intracellular widespread bacteria of the genera Chlamydia, Mycoplasma, Rickettsia, Yersinia and Legionella [12–14]. Their strategies to modulate the host epigenome in order to overcome the host defense for their persistence are reviewed in the present study. Int. J. Mol. Sci. 2020, 21, 4573; doi:10.3390/ijms21134573 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 2 of 15 strategies to modulate the host epigenome in order to overcome the host defense for their Int.persistence J. Mol. Sci. 2020 are, 21 reviewed, 4573 in the present study. 2 of 16 Figure 1. Strategies exploited by pathogens to modulate host epigenome. Figure 1. Strategies exploited by pathogens to modulate host epigenome. 2. Mycobacterium Tuberculosis 2. 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