Table 1.
Leishmania plasticity and Leishmania-induced host epigenetic alterations.
| Epigenetic regulator | Modification | Condition | Effect | Reference |
|---|---|---|---|---|
| EPIGENETIC REGULATION IN LEISHMANIA | ||||
| Base J | ↑ | L. major | Parasite survival | (15) |
| H2A.Z, H2B.V | ↑ | L. major | Parasite survival | (16) |
| HAT2 | ↑ | L. donovani | Cyclins ↑, parasite survival | (17) |
| HAT3 | ↑ | L. donovani | Parasite survival | (18) |
| HAT4 | ↑ | L. donovani | Cyclins ↑, parasite survival | (19) |
| HDAC | ↑ | L. infantum logarithmic phase promastigotes versus intracellular amastigotes | Adaptation of amastigotes to phagolysosomal milieu | (20) |
| Sirtuin 2 | ↑ | Amp BR - L. donovani | ROS ↓, apoptosis ↓ | (21) |
| LEISHMANIA-INDUCED HOST EPIGENETIC ALTERATIONS | ||||
| FL1 methylation | ↓ | L. braziliensis infected møs from skin lesions | FLI gene expression | (22) |
| IRAK2 DNA methylation at CpG sites | ↑ | L. donovani infected møs | IRAK2 mRNA ↓, NF-κB ↓, immune silencing | (23) |
| LARS2 related CpG site methylation | ↑ | L. donovani infected møs | LARS mRNA ↓, mTORC1 ↓, 4E-BP1 ↑, parasite proliferation | (23) |
| CDC42EP3 methylation at CpG sites | ↓ | L. donovani infected møs | CDC42EP3 mRNA ↑, Progression of infection | (23) |
| HDAC4 | ↑ | L. donovani infected møs | Phagolysosomal formation, amastigote survival | (23) |
| HDAC11 | ↑ | Imipramine treated SbR-L. donovani infected human møs | IL-12/IL-10 ratio ↑, parasite burden↓ | (24) |
| HDAC1 | ↑ | L. amazonensis infected møs | iNOS ↓, parasite survival | (25) |
| miRNA-294,−721 | ↑ | L. amazonensis infected møs | Targets NOS-2, L-Arginine metabolism, NO ↓, parasite establishment | (26) |
| miRNA-210 | ↑ | L. major infected møs | Activates hypoxia inducible factor-1α, parasite survival | (27), (28) |
| miRNA-129- 5p,−101c | ↓ | L. major infected møs | Autophagy ↑, infection↓ | (28) |
| miRNA-25, - 26a,−140, - 155, let-7a | ↑ | L. major infected human møs | Corresponding chemokine targets ↓ (CCL5, CXCL10, CXCL11, CXCL12, CCL2) | (29) |
| miRNA-155 | ↑ | L. major infected human DCs | PU.1 (SPI1) ↑, TGF-β signaling | (30) |
| let7a/b | ↓ | L. major infected human DCs, møs | Pro-inflammatory cytokines IL-12↓ | (30) |
| miRNA-193b,−671 | ↑ | Lesions from L. braziliensis infected patients | CD40, TNFR, inflammatory response, faster wound healing | (31) |
| miRNA-361- 3p | ↑ | Skin lesions from L. braziliensis infected patients | Therapeutic failure, healing time ↑, prognostic biomarker | (31) |
| miRNA-30A- 3p | ↑ | L. donovani infected THP-1, HMDMs | Autophagy ↓, promotes parasite survival | (32) |
| miRNA122 | ↓ | L. donovani infected murine hepatocytes | Serum cholesterol ↓, maintains infection | (33) |
| miRNA-30c | ↓ | DBA-treated intramacrophagic L. donovani amastigotes | Inhibits proliferation and virulence | (32) |
| miRNA-151a | ↓ | DBA-treated intramacrophagic L. donovani amastigotes | Mitochondrial dysfunction | (32) |
| miRNA-6540 | ↓ | L. donovani infected møs | Promotes intracellular parasite survival | (34) |
| miRNA- 3473f | ↓ | L. donovani infected møs | Autophagy ↓, role in pathogenesis | (34) |
| miRNA- 6973a | ↑ | L. donovani infected møs | IL-12 ↓, Th1 → Th2, parasite survival | (34) |
| miRNA-3620 | L. donovani infected møs | Iron homeostasis genes, iron in cytoplasm, parasite survival | (34) | |
| miRNA-3620,−6385 | ↑ | L. donovani infected møs | Hypoxia inducing genes ↓, macrophage effector functions ↓, parasite survival | (34) |
| miRNA-763,−1264,−3473f | ↓ | L. donovani infected møs | ABC transporters ↑, drug efflux ↑, resistance | (34) |
| miRNA-21 | ↑ | L. donovani infected human DCs | SMAD7 ↓, TGF-β signaling | (30) |
| miRNA- 146b-5p | ↑ | L. donovani infected human DCs | TRAF6 ↑, TGF-β signaling | (30) |
| let7a/b | ↑ | L. donovani infected human DCs, møs | Target pro-inflammatory genes, pro-inflammatory cytokines IL-12 ↓ | (30) |
| miRNA-511 | ↑ | L. donovani infected human DCs | TLR4 activation | (30) |
| miRNA-488i | ↑ | SbR-L. donovani infected møs | MyD88 ↓, IL-10/IL-12 ↑ ratio, parasite number ↑ | (35) |
| miRNA-34a | ↓ | L. donovani infected human møs | c-myc ↑, M2 mø activation, attenuates parasite survival | (36) |
| miRNA-155 | ↑ | L. infantum infected J774 møs | Susceptibility to Sb ↓ | (25) |
| miRNA-191,−374 | ↑ | L. infantum infected dog PBMCs | Parasite load ↑ | (37) |
| miRNA-150 | ↓ | L. infantum infected dog PBMCs | Parasite load ↑ | (37) |
HDAC, Histone deacetylase; IRAK2, interleukin-1 receptor associated kinase 2; LARS, leucyl-tRNA synthetase; Amp, BR Amphotericin B resistant; møs, macrophages; HMDMs, Human monocyte derived macrophages; DBA, dibenzalacetone; ABC, ATP-binding cassette; DCs, Dendritic cells; I, inhibitor; SbR, Antimony resistant; Sirtuins, Silent Information Regulator.