Table 1.
Modification of DNA methylation induced by bacteria and its effects on immune responses.
| Bacteria | Effect on DNA methylation | Impact on immune response | References |
|---|---|---|---|
| Gut microbiota | Altered DNA methylation in IECs | Changed expression of genes related to immunity and metabolism in IECs | (135–137) |
| Hypermethylation of TLR4 in IECs | Suppressed response to LPS and commensal microbiota, maintaining intestinal homeostasis | (138, 139) | |
| Demethylation in IECs mediated by TET2/TET3 | Maintained intestinal homeostasis and inhibition of acute inflammation in experimental colitis | (137, 140) | |
| Polymicrobial | Altered DNA methylation in whole blood leukocytes | Changed gene expression in whole blood leukocytes of septic patients | (141, 142) |
| Altered DNA methylation in monocytes | Increased IL-10 and IL-6 levels and organ dysfunction in septic patients | (143) | |
| Altered expression of DNMTs and TETs | Increased disease severity in septic patients or experimental septic mice | (130, 144, 145) | |
| Helicobacter pylori | Aberrant DNA methylation in gastric mucosae caused by infection induced inflammation | Increased risk of gastric cancer | (134, 146–149) |
| Aberrant DNMT activity in gastric tissues | Increased susceptibility to infection | (55, 150) | |
| Mycobacterium tuberculosis | Altered DNA methylation in dendritic cells and macrophages in vitro and in vivo | Altered transcription of genes involved in immune response | (11, 151, 152) |
| Aberrant DNA methylation in monocytes | Increased disease severity | (153–155) | |
| Demethylation at the promoter region of Nlrp3 in macrophages | Increased NLRP3 inflammasome activation and downstream release of IL-1β and IL-18 | (156) | |
| Aberrant methylation at the TLR2 promoter in human blood leukocytes | Negatively regulated TLR2 expression; increased bacterial burden and disease severity | (154) | |
| Escherichia coli | Aberrant DNA methylation by altered DNMT activity in T cells | Dysregulation of immune responses to bacterial infection induced lung injury | (157, 158) |
| Increased DNMT1 activity in uroepithelial cells | Downregulation of CDKN2A (tumor suppressor gene) and increased risk of bladder cancer consequently | (159, 160) | |
| Decreased DNMT3A activity in porcine mammary epithelial cells | Enhanced immune response | (161) | |
| Downregulation of TET1 in THP1 macrophages | Reduced NF-κB signaling pathway and inhibition of macrophage M1 polarization | (162) | |
| Salmonella | Altered DNA methylation in chicken cecum and blood leukocytes | Changed expression of immune and metabolic genes | (163, 164) |
| Enhanced DNA methylation at the promoters of TLR4, TLR21 and TLR2-1 in chicken blood leukocytes | Reduced MyD88 signaling and increased susceptibility to Salmonella enterica | (165, 166) | |
| Pseudomonas aeruginosa | Altered DNA methylation at NODAL in bronchial epithelial cells | Changed airway homeostasis | (167) |
| Aberrant function of DNMT3B | Increased susceptibility to infection | (168, 169) | |
| Methicillin-resistant Staphylococcus aureus | Reduced DNMT3A in macrophage and neutrophils | Reduced IL-10 production and increased inflammatory responses in patients; Increased susceptibility and mortality in murine models | (170) |
| Modified DNA methylation signatures in circulating immune cells | Increased disease severity in patients | (171) | |
| Campylobacter rectus | Hypermethylation of Igf2 in mouse placenta | Down-regulation of Igf2 and aberrant placental growth | (172) |
| Porphyromonas gingivalis | Decreased DNMT1 expression in gingival epithelial cells | Increased antibacterial responses by promoting β-defensin 2 and CC chemokine ligand 20 expression | (173) |
| Anaplasma phagocytophilum | DNA hypermethylation in neutrophils potentially by promoting DNMT3A expression | Reduced neutrophil antibacterial functions | (174) |
| Bacterial products | Effect on DNA methylation | Impact on immune response | References |
| LPS | Aberrant DNA methylation at TLRs, inflammatory cytokines (IL6, TNF) | Dysregulation of cellular responses to LPS stimulation | (175–178) |
| Increased DNMT1 activity in macrophages | Enhanced inflammatory responses by hypermethylation of anti-inflammatory factors such as KLF4, miR-145 and SOCS3 | (178–180) | |
| Downregulation of TET1 in macrophages | Inhibition of NF-κB signaling and decreased inflammatory responses | (162) | |
| Increased Tet2 expression in myeloid cells | Decreased IL-6 production and reduced inflammation in vivo | (63, 122) | |
| Staphylococcal enterotoxin B | Modified DNA methylation of some genes with important roles in immunity in nasal polyp explants | Potentially altered immune responses related to T-cell maturation/activation | (181) |
| Peptidoglycan and lipoteichoic acid | Suppressed DNMT activity and hypomethylation of global DNA | Enhanced inflammatory responses | (182) |
| Rv2966c from Mycobacterium tuberculosis; Mhy1, Mhy2, and Mhy3 produced by Mycoplasma hyorhinis | Hypermethylation of host genes by acting as DNA methyltransferase | Interference with host immune response | (183–185, 212) |
| Extracellular vesicles secreted by P. aeruginosa | Modified DNA methylation at enhancers of immune-related genes in human lung macrophages | Abnormal innate immune response | (203) |
| Bacterial metabolite folate | Increased DNMT activity with altered DNA methylation in host cells | Unknown | (186) |
IECs, intestinal epithelial cells; TLR, Toll-like receptors; LPS, lipopolysaccharide; DNMT, DNA methyltransferase; TET, ten-eleven translocation methylcytosine; KLF4, Krüppel-like factor 4; SOCS3, Suppressor of cytokine signaling 3; IL, interleukin; TNF, tumor necrosis factor.