The Role of Epigenetics in Infectious Diseases

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Background

Human chromatin modifications regulate tissue-specific gene expression patterns that respond to various stimuli. These dynamic epigenetic variations and transgressions have been associated with cancer, neurological, psychiatric, and autoimmune disorders. Extensive research, especially in the cancer field, has broadened our understanding of these processes leading to the clinical use of FDA-approved drugs, such as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors for hematologic cancers. Increasing literature points towards a significant role of epigenetic alternations in genomes of both host and pathogens in determining outcomes of infections. Host epigenetic factors have been shown to play an important role throughout the viral life cycle and have been implicated in the pathogenesis of several viral infections, such as human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV), hepatitis viruses, herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV). Many protozoan parasites and pathogenic fungi use epigenetic machinery for antigenic variation as the major strategy to evade the host immune defenses. These ever-changing ‘cloaks of invisibility’ enable the pathogens to persist in the hosts. In addition, infections can result in epigenetic changes to host cells resulting in impairment of host cellular and immune defenses. It is though not clear the extent epigenetics plays on immune cells and genes within infectious diseases.

While there is evidence that infections can result in epigenetic changes to host immune cells, it is not always clear whether the changes are directly induced by the pathogen or are the result of the response of the host cell to infection. Also, while epigenetic changes themselves may have been characterized, the mechanism or molecules that mediate these changes and their origin are not always known. Recent technological advancements have allowed considerable progress in understanding the role played by epigenetic mechanisms in the pathogenesis of infectious diseases. Since epigenetic changes are not detectable at the DNA sequence level, epigenome mapping, which explores genome-wide chromatin modification patterns, may help in discovering disease-causing genes and in developing novel diagnostic and treatment strategies. For example, potential immune genes related to Levofloxacin resistance in Mycobacterium tuberculosis have been identified based on transcriptome and methylome sequencing. Genome-wide DNA methylation patterns in dendritic cells infected with Mycobacterium tuberculosis have also allowed for the identification of methylation changes in specific immune genes differentially expressed in response to mycobacterium infection.

This Research Topic aims at bringing together contributions covering different epigenetic processes involved in the host and pathogen interactions helping to drive forward the understanding of the role of epigenetics in immunology, pathogenesis, and possible clinical intervention of infectious diseases.

In this Research Topic, we welcome Original Research Articles, Reviews, and Methods that apply modern technical approaches to study the role of epigenetics in the pathogenesis of infectious diseases and to identify new potential therapeutic strategies. We especially aim to cover:

(1) Next-generation sequencing (NGS) both for genome-wide and targeted analysis to detect pathogen-induced epigenetic modulations in the immune system of the host.
(2) Identification of epigenetic immune markers associated with infectious disease outcomes including occurrence, progression, and pathogen-induced cancers.
(3) Single-cell epigenome and transcriptome analysis, and other approaches to map cellular networks driving susceptibility to infectious diseases.
(4) Epigenetic mechanisms of gene regulation in pathogenic viruses, fungi, bacteria, and parasites.
(5) Epigenetic mechanisms of drug resistance.
(6) Targeting epigenetic machinery for the development of potential new drugs.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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