# The Epigenetic Battleground: Host Chromatin at the Core of Infection

**Authors:** Fabrício Castro Machado, Nilmar Silvio Moretti

PMC · DOI: 10.3390/epigenomes10010013 · Epigenomes · 2026-02-15

## TL;DR

This paper explores how chromatin regulation during infections is a battleground between host defenses and pathogen strategies, offering insights into potential new therapies.

## Contribution

The paper provides a comprehensive review of how different pathogens manipulate host chromatin and highlights new techniques for studying these interactions.

## Key findings

- Pathogens use various strategies to reprogram host chromatin for infection success.
- Host cells activate immune responses through chromatin dynamics during infections.
- New omics technologies are revealing detailed chromatin changes during infections.

## Abstract

Chromatin dynamics are usually modulated by histone epigenetic post-translational modifications, which rapidly and reversibly govern accessibility and transcriptional responsiveness. During microbial infection, this regulatory layer becomes a highly contested interface where host defense mechanisms and pathogen-driven subversion strategies converge and compete. Many infectious agents exploit chromatin to reprogram gene expression, creating cellular environments that are conducive to infection, proliferation, and persistence. Diverse strategies have been described for viruses, bacteria, fungi, protozoa and nematodes, including the direct secretion of acetyltransferases and methyltransferases, interference with host chromatin-binding proteins, subcellular localization of transcriptional factors or epigenetic regulators, and metabolic availability manipulation. Concurrently, host cells activate immune and stress-response genes to mount rapid, adaptable antimicrobial responses. Recent advances in genome-wide, single-cell, and spatial omics profiling have begun to reveal the temporal and cell-type-specific dynamics of the host genome at the core of infection. This review synthesizes current insights into how chromatin is rewired by the major categories of pathogens during infection, highlighting representative case studies across infective agents and the functional consequences for immunity and cell fate. In addition, we discuss emerging techniques for epigenomic and transcriptomic data collection, and the potential of targeted host-directed therapeutic strategies. Chromatin regulation is thus a promising field of study and a possible target for next-generation interventions.

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, BDP1 (BDP1 general transcription factor IIIB subunit) [NCBI Gene 55814] {aka DFNB112, HSA238520, TAF3B1, TFC5, TFIIIB'', TFIIIB150}, BCKDHA (branched chain keto acid dehydrogenase E1 subunit alpha) [NCBI Gene 593] {aka BCKDE1A, MSU, MSUD1, MSUD1A, OVD1A}, KDM3A (lysine demethylase 3A) [NCBI Gene 55818] {aka JHDM2A, JHMD2A, JMJD1, JMJD1A, TSGA}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, LANA [NCBI Gene 4961527], IVNS1ABP (influenza virus NS1A binding protein) [NCBI Gene 10625] {aka ARA3, FLARA3, HSPC068, IMD70, KLHL39, ND1}, IAA16 (indoleacetic acid-induced protein 16) [NCBI Gene 819633] {aka F7O18.22, F7O18_22, indoleacetic acid-induced protein 16}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}
- **Diseases:** root rot (MESH:D005535), viremia (MESH:D014766), Cyst nematodes (MESH:D009349), pneumonia (MESH:D011014), microbial infection (MESH:D015163), mastitis (MESH:D008413), neutrophil dysfunction (MESH:C564942), Listeria infection (MESH:D008088), injury to (MESH:D014947), chronic inflammation (MESH:D007249), Legionella (MESH:D007877), poisoning (MESH:D011041), Leishmania amazonensis infection (MESH:D007896), cancer (MESH:D009369), bacterial (MESH:D001424), Brucella infection (MESH:D002006), chronic (MESH:D002908), infectious (MESH:D003141), HIV-infected (MESH:D015658), T. cruzi infection (MESH:D014355), Viral infection (MESH:D014777), diarrheal disease (MESH:D004403), Infection (MESH:D007239), COVID-19 (MESH:D000086382)
- **Chemicals:** acetyl-CoA (MESH:D000105), HC toxin (MESH:C037654), LPS (MESH:D008070), ATP (MESH:D000255), auxin (MESH:D007210), SCFA (MESH:D005232), reactive oxygen species (MESH:D017382), NAD+ (MESH:D009243), alpha-ketoglutarate (MESH:D007656), 10A07 (-), coenzyme A (MESH:D003065), butyrate (MESH:D002087)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Heterodera schachtii (species) [taxon 97005], Salmonella enterica (species) [taxon 28901], Phytophthora sojae (species) [taxon 67593], Chlamydia trachomatis (species) [taxon 813], Yersinia pestis (species) [taxon 632], Toxoplasma gondii (species) [taxon 5811], Human immunodeficiency virus 1 (no rank) [taxon 11676], Trypanosoma cruzi (species) [taxon 5693], Glycine max (soybean, species) [taxon 3847], Human alphaherpesvirus 1 (Herpes simplex virus type 1, no rank) [taxon 10298], Listeria (genus) [taxon 1637], Mus musculus (house mouse, species) [taxon 10090], Echinamoeba (genus) [taxon 136449], Bacillus anthracis (anthrax bacterium, species) [taxon 1392], Vibrio parahaemolyticus (species) [taxon 670], Francisella tularensis (species) [taxon 263], Human gammaherpesvirus 8 (no rank) [taxon 37296], Agrobacterium tumefaciens (species) [taxon 358], Legionellales (order) [taxon 118969], Leishmania donovani (species) [taxon 5661], Legionella pneumophila (species) [taxon 446], Influenza A virus (no rank) [taxon 11320], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Listeria monocytogenes (species) [taxon 1639], Viruses (acellular root) [taxon 10239], Bipolaris zeicola (species) [taxon 5017], Aeromonas salmonicida (species) [taxon 645], Ehrlichia chaffeensis (species) [taxon 945], Homo sapiens (human, species) [taxon 9606], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Staphylococcus aureus (species) [taxon 1280], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Mycobacterium tuberculosis (species) [taxon 1773]
- **Cell lines:** THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006)

## Full text

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## Figures

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## References

204 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937675/full.md

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Source: https://tomesphere.com/paper/PMC12937675