Table 2.
Mycobacterium infection results in alterations in a large number of microRNAs within the host cells these up‐ and down‐regulations are highly dependent upon the infecting Mycobacterial species and responding host cell types to produce context‐dependent cellular effects
| miRNA | Status a | Targets | Cell types | Mycobacterium species | Comment/mechanism(s) of action |
|---|---|---|---|---|---|
| Undetermined | |||||
| 1. miR‐125b | – | κB‐Ras2 3′UTR | Primary human mϕ | – | Estradiol represses NF‐κB activation through induction of κB‐Ras2 |
| 2. miR‐129 | – | SP3 | Predicted | Mycobacterium tuberculosis | SP3 maintains M1/M2 plasticity |
|
3. miR‐150↓; miR‐485‐3p↑ |
– | – | THP‐1 | Mtb Beijing/W, non‐Beijing/W clinical strains | Alterations in the Wnt pathway, insulin pathway, TGF‐β pathway, and glycosaminoglycan biosynthesis |
| 4. miR‐33 | – | NOD2 | Predicted | Mycobacterium tuberculosis | Downregulation of NOD2 dampens the inflammatory response |
| 5. miR‐365 | – | IL‐6 | HEK293 | – | Post‐transcriptional level regulation of IL‐6 by miRNA‐365 |
| 6. miR‐455‐5p | – | SOCS3 | Predicted | Mycobacterium tuberculosis | The expression of miR‐455‐3p downregulate SOCS3 expression which promotes M2 phenotype |
| 7. Sp110 | – | miR‐125a; miR‐146a; miR‐155; miR‐21a; miR‐99b | RAW264.7 | Mycobacterium tuberculosis H37Ra | Sp110‐mediated macrophage resistance to Mtb underlines the inhibiting of multiple miRNAs and modulating host immune response |
| Upregulated | |||||
| 8. hsa‐let‐7b‐5p | ↑ | APO‐1/FAS/CD95 | THP‐1 | Mycobacterium tuberculosis | hsa‐let‐7b‐5p helps intracellular survival of Mtb in THP‐1 cells by downregulating Fas protein level |
| 9. hsa‐miR‐144‐5p | ↑ | DRAM2 | TB patients; PBCs; Tissues | Mycobacterium tuberculosis | Inhibiting anti‐bacterial autophagy |
| 10. miR let‐7e | ↑ | CASP3 | Human MDMs | Mycobacterium avium | Interfering with the regulation of apoptosis |
| 11. miR‐106b‐5p | ↑ | Cathepsin S | Human mϕ | Mycobacterium tuberculosis | Mtb avoids exposure to degradative enzymes in the endocytic pathway |
| 12. miR‐1178 | ↑ | TLR4 | Human mϕ; HTP‐1; U937 cells | Mycobacterium tuberculosis | Reduction of pro‐inflammatory cytokines‐ IFN‐γ, IL‐6, IL‐1β, and TNF‐α |
| 13. miR‐124 | ↑ |
MyD88; TRAF6; TLR6 |
TB patient Leucocytes; RAW264.7 AM |
Mycobacterium tuberculosis; Mycobacterium bovis (BCG) |
Negative regulatory role of miR‐124 in the fine‐tuning inflammatory response in alveolar macrophages |
| 14. miR‐125a | ↑ | UVRAG | RAW264.7; J774A.1 | Mycobacterium tuberculosis | Inhibiting autophagosome formation thereby promoting intracellular growth of Mycobacterium tuberculosis |
| 15. miR‐129‐3p | ↑ | Atg4b | RAW264.7 | Mycobacterium tuberculosis | Inhibiting autophagy favors Mtb survival |
|
16. miR‐132; miR‐26a |
↑ | p300 | Primary human mϕ | Mycobacterium tuberculosis | Limiting macrophage responses to IFN‐γ |
| 17. miR‐140 | ↑ | TRAF6 | TB patient PBMCs; THP‐1 and U937 | Mycobacterium tuberculosis | miR‐140 promotes Mtb survival by suppressing pro‐inflammatory cytokines production |
| 18. miR‐142‐3p | ↑ | N‐Wasp | J774A.1; Primary Human mϕ | Mycobacterium smegmatis | Alterations of actin filament assembly affecting other early events of phagolysosome biogenesis |
|
19. miR‐143; miR‐365 |
↑ | c‐Maf, Bach‐1, and Elmo‐1 | BMDMs | Mtb clinical Beijing strain HN878 | miRNA‐mediated regulation of c‐Maf, Bach‐1, and Elmo‐1 in Mtb‐infected (IL‐4/IL‐13) macrophages |
| 20. miR‐144 | ↑ | ‐ | TB patients PBMCs | Mycobacterium tuberculosis | Inhibiting TNF‐α and IFN‐γ production and T‐cell proliferation |
| 21. miR‐144‐3p | ↑ | ATG4a | RAW264.7 |
Mycobacterium bovis (BCG) Mycobacterium tuberculosis |
Inhibiting the formation of autophagosomes. |
| 22. miR‐145 | ↑ | TIRAP | MDMs | Virulent H37Rv | Elicited only by virulent H37Rv infection |
| 23. miR‐146 | ↑ | IRAK1; TGFBR2 | Bovine mϕ cell line (Bomac) | Mycobacterium bovis | Post‐transcriptional regulation of IL‐1, TLR signalling via IRAK1 |
| 24. miR‐146a | ↑ | TRAF6 | RAW264.7; BMDMs | Mycobacterium tuberculosis | Suppressing nitric oxide production via iNOS |
| 25. miR‐146a | ↑ | – | Human PBMCs | Mycobacterium abscessus | Mycobacterium abscessus may promote a neutrophil‐dependent growth niche |
| 26. miR‐155 | ↑ | ATG3 | Human DC | Mycobacterium tuberculosis | Subverting autophagy |
| 27. miR‐155 | ↑ | SHIP1 | Mϕ |
Mycobacterium tuberculosis Mycobacterium bovis (BCG) |
miR‐155 regulating macrophage survival and T‐cell expansion through SHIP1; miR‐155 repressing the expression of SHIP1 and modulating ROS production |
| 28. miR‐155 | ↑ | Rheb | BMDMs; RAW264.7 | Mycobacterium tuberculosis | Induction of miR‐155, in turn, activates autophagy by targeting Rheb |
| 29. miR‐155 | ↑ | FOXO3 | THP‑1; TB Patients PBMCs | Mycobacterium tuberculosis | Apoptosis inhibition through regulating FOXO3 target genes |
|
30. miR‐155; miR‐ 31 |
↑ | PP2A (Ppp2r5a) | RAW264.7; BMDMs | Mycobacterium bovis (BCG) | Mycobacterium bovis BCG‐induced miR‐155 and miR‐ 31 are required for activating the WNT‐SHH pathway and autophagy regulation |
| 31. miR‐1958 | ↑ | Atg5 | RAW264.7 | Mycobacterium tuberculosis | Inhibiting autophagy by interacting with Atg5 and supporting intracellular Mtb survival |
| 32. miR‐199a | ↑ | TBK1 | J774A.1; BMDM | Mycobacterium bovis | Suppressing maturation of autophagosomes and interferon‐β (IFN‐β) production |
| 33. miR‐206 | ↑ | TIMP‐3 | THP‐1 | Mycobacterium tuberculosis | miR‐206 is a regulator of inflammation and MMP‐9 by targeting TIMP3 |
| 34. miR‐21 | ↑ | PFK‐M | BMDM; Human MDM; RAW267.4 |
Mycobacterium tuberculosis H37Ra, H37Rv |
Mtb limits glycolysis in host macrophages through sustained induction of anti‐inflammatory miR‐21 |
| 35. miR‐21 | ↑ | IL‐12p35; Bcl‐2 | BMDMs; BMDCs | Mycobacterium bovis (BCG) | Modulating anti‐mycobacterial TH1 response inefficacy of BCG vaccination |
| 36. miR‐223 | ↑ | CXCL2; CCL3; IL‐6 | TB patients; Murine myeloid cells | Mycobacterium tuberculosis | miR‐223 regulating leucocyte chemotaxis via chemoattractants |
| 37. miR‐22‐3p | ↑ | Unknown | TB patient | Mycobacterium tuberculosis | Plasma biomarker |
| 38. miR‐23a‐5p | ↑ | TLR2 | RAW264.7 | Mycobacterium tuberculosis | Modulation of TLR2/MyD88/NF‐κB signalling |
| 39. miR‐27a | ↑ | CACNA2D3 | Human PBMCs | Mycobacterium tuberculosis | Inhibiting autophagosome formation and promoting the intracellular survival of Mtb |
| 40. miR‐27b | ↑ | Bag2 | RAW264.7; HEK293T | Mycobacterium tuberculosis | miR‐27b positively regulates apoptosis by directly targeting Bag2 and increasing the activity of the p53–ROS signalling pathway |
| 41. miR‐29a | ↑ | CASP7 | Human MDMs | Mycobacterium avium | Interfering with the regulation of apoptosis |
| 42. miR‐30a | ↑ | MyD88 | THP‐1 cells | Mycobacterium tuberculosis H37Rv | Inhibiting TLR/MyD88 activation and cytokine (TNF‐α, IL‐6, IL‐8) expression |
|
43. miR‐31; miR‐150 |
↑ | MyD88 | TB patients PBMCs; BMDMs | Mycobacterium bovis (BCG) | Sonic hedgehog signalling‐responsive miR‐31 and miR‐150 target MyD88 suppressing TLR2 signalling |
| 44. miR‐3178 | ↑ | TRAF‐3 | THP‐1 | Mycobacterium tuberculosis H37Rv | More research is required for inferring definitive roles of this miRNA in the context of Mtb infection |
| 45. miR‐32‐5p | ↑ | FSTL1 | THP‐1 and U937 | Mycobacterium tuberculosis | TLR‐4/miRNA‐32‐5p/FSTL1 axis modulating host defence against mycobacterial infection |
| 46. miR‐33 | ↑ | ABCA1; ATG5; LAMP1 | THP‐1 | Mycobacterium tuberculosis | Target's autophagy suppression, and compromisation of lysosomal function, and lipid homeostasis |
| 47. miR‐3619‐5p | ↑ | Cathepsin S (CTSS) | THP‐1 | Mycobacterium bovis (BCG) | CTSS targeting by miR‐3619‐5p impairs the degradation of autophagic substrates thus blocking autophagosome‐lysosome processing |
| 48. miR‐381‐3p | ↑ | CD1c | TB patient DCs | Bacillus calmette‐Guérin (BCG) | Suppression of lipid antigen presentation and induction of IL‐10 |
| 49. miR‐579 | ↑ | SIRT1; PDK1 | Human mϕ | Mycobacterium tuberculosis | Macrophage cell death and apoptosis |
| 50. miR‐‐5p | ↑ | Bcl‐2; TLR4 | RAW264.7 and THP‐1 | Mycobacterium tuberculosis | Enhances Mtb survival and apoptosis, by attenuating the secretion of inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) |
| 51. miR‐708‐5p | ↑ | TLR4 | Human mϕ | Mycobacterium tuberculosis | Reduction of pro‐inflammatory cytokines‐ IFN‐γ, IL‐6, IL‐1β, and TNF‐α |
| 52. miR‐889 | ↑ | TWEAK | Latent TB patients | Mycobacterium tuberculosis | miR‐889 inhibits autophagy via suppression of TWEAK expression |
| 53. miR‐99b | ↑ |
TNFRSF4/ OX40; TNF‐α |
DC and mϕ | Mycobacterium tuberculosis H37Rv | The knockdown of miR‐99b in DCs reduces Mtb growth owing to increasing levels of IL‐1β, TNF‐α |
| Downregulated | |||||
| 54. miR let‐7f | ↓ | A20/TNFAIP3 | RAW264.7 | Mycobacterium tuberculosis | Mycobacterium tuberculosis macrophage infection leads to ESAT‐6‐dependent miRNA let‐7f downregulation |
| 55. miR‐125b | ↓ | TNF mRNA | Human mϕ | Mycobacterium smegmatis | TLR2‐dependent MAPK p38 and the PI3K/Akt pathway with the production of steady‐state TNF mRNA |
| 56. miR‐144 | ↓ | Tpl2/MAP3K8 | MDMs | Mycobacterium tuberculosis | Suppression of TNF‐α, IL‐1β, and IL‐6 via the ERK1/2 pathway |
| 57. miR‐17 | ↓ | ULK1; Beclin 1; ATG7; MCL‐1 ATG16L1; p62; STAT3 | RAW264.7 | Mycobacterium tuberculosis | miR‐17/PKC δ/STAT3 axis regulates autophagy during Mtb infection |
| 58. miR‐20b | ↓ | NLRP3 | TB patient mϕ | Mycobacterium tuberculosis | Deactivating the NLRP3/caspase‐1/IL‐1β pathway in TB mice; Mitigating the inflammation and pyroptosis |
| 59. miR‐20b‐5p | ↓ | Mcl‐1 | RAW264.7 | Mycobacterium tuberculosis | Enhancing Mtb survival via attenuating the cell apoptosis by Mcl‐1 upregulation |
| 60. miR‐26a | ↓ | KLF4 | RAW264.7 | Mycobacterium tuberculosis | Facilitates upregulation of KLF4 consequently increases arginase and decreases iNOS activity; affecting the trafficking of Mtb to lysosomes |
| 61. miR‐26b | ↓ | TAK‐1 | THP‐1 | Mycobacterium tuberculosis | miR‐26b suppresses the TNFα‐induced NF‐κB signalling in THP‐1 cells |
| 62. miR‐27a | ↓ | TAB 2/3 | RAW264.7; BMDMs | Mycobacterium avium subspecies paratuberculosis | Inhibiting the activation of the MAPK‐p38 signalling |
| 63. miR‐27a | ↓ | IRAK4 | THP‐1 | Mycobacterium tuberculosis | miR‐27a inhibiting the release of inflammatory factors and promoting mycobacterial survival |
| 64. miR‐29 | ↓ | IFN‐γ mRNA | NK cell; CD4+; CD8+ T cells | Mycobacterium bovis (BCG) | miR‐29 suppresses IFN‐γ production by directly targeting IFN‐γ mRNA |
| 65. miR‐3178 | ↓ | TRAF‐3 | GES‐1 cells | Helicobacter pylori | Contrasting to Mtb infection, miR‐3178 is downregulated, controls inflammation, and gastric carcinogenesis in this model |
a
Status of miRNAs indicating Downregulation (↓) and Upregulation (↑)