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      The Role of Host Cell DNA Methylation in the Immune Response to Bacterial Infection

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          Abstract

          Host cells undergo complex transcriptional reprogramming upon infection. Epigenetic changes play a key role in the immune response to bacteria, among which DNA modifications that include methylation have received much attention in recent years. The extent of DNA methylation is well known to regulate gene expression. Whilst historically DNA methylation was considered to be a stable epigenetic modification, accumulating evidence indicates that DNA methylation patterns can be altered rapidly upon exposure of cells to changing environments and pathogens. Furthermore, the action of proteins regulating DNA methylation, particularly DNA methyltransferases and ten-eleven translocation methylcytosine dioxygenases, may be modulated, at least in part, by bacteria. This review discusses the principles of DNA methylation, and recent insights about the regulation of host DNA methylation during bacterial infection.

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          Most cited references215

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Functions of DNA methylation: islands, start sites, gene bodies and beyond.

            DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.
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              Recognition of microorganisms and activation of the immune response.

              The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections. The innate immune system consists of functionally distinct 'modules' that evolved to provide different forms of protection against pathogens. It senses pathogens through pattern-recognition receptors, which trigger the activation of antimicrobial defences and stimulate the adaptive immune response. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. The connections between the various immune components are not fully understood, but recent progress brings us closer to an integrated view of the immune system and its function in host defence.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                29 July 2021
                2021
                : 12
                : 696280
                Affiliations
                [1] 1Center of Experimental & Molecular Medicine, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam , Amsterdam, Netherlands
                [2] 2Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam , Amsterdam, Netherlands
                [3] 3Division of Infectious Diseases, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam , Amsterdam, Netherlands
                Author notes

                Edited by: Smita Kulkarni, Texas Biomedical Research Institute, United States

                Reviewed by: Krishnendu Mukherjee, University Hospital Münster, Germany; Xue-Ming Zhang, Jilin University, China; Zhiqin Wang, Central South University, China; Taiping Chen, University of Texas MD Anderson Cancer Center, United States; Enass Abdel-Hameed, University of Cincinnati, United States

                *Correspondence: Wanhai Qin, w.qin@ 123456amsterdamumc.nl

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.696280
                8358789
                34394088
                d937d61f-5a36-440c-ade1-be6d19ec5e55
                Copyright © 2021 Qin, Scicluna and van der Poll

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 April 2021
                : 15 July 2021
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 215, Pages: 17, Words: 7843
                Categories
                Immunology
                Review

                Immunology
                dna methylation,immune response,bacteria,infection,mechanism,review
                Immunology
                dna methylation, immune response, bacteria, infection, mechanism, review

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