The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Innate Immunity and Toll-like Receptors
1.2. The Diversity of TLRs
1.3. TLR2, an Important Member of the TLR Family
2. Regulation of TLR2 Signaling
3. TLR2 Function in Immune Responses to Mycobacterial Infection
3.1. Tuberculosis and Non-Tuberculosis Diseases Caused by Mycobacteria
3.2. Which TLRs Play a Role in Defense against Mycobacteria?
3.3. TLR2 Recognizes Mycobacterial Components
3.4. TLR2 Is Associated with the Susceptibility to Infection by Various Mycobacteria
4. TLR2 Function in Mediating the Host–Mycobacterial Interaction
4.1. Macrophage–Mycobacterial Interactions
4.2. Neutrophil–Mycobacterial Interactions
5. Therapeutic Targeting of TLR2 Signaling in Diseases
5.1. The Application of TLR2 Ligands in Mycobacterial Infectious Diseases
5.2. TLR2 as a Therapeutic Target in the Other Diseases
6. Zebrafish as a Model to Investigate TLR2 as a Therapeutic Target
6.1. General Advantages of the Zebrafish Larval Model
6.2. New Insights of the Tlr2 Function Learned from the Zebrafish Model
7. Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Spp | Ligand(s) | Abbreviation | PRRs | Accessory Molecules | Observations | Ref. |
---|---|---|---|---|---|---|
M. tuberculosis | Lipoproteins | |||||
19-kDa lipoprotein (Rv3763) | LpqH | TLR2/1 | CD14 | Inhibits MHC expression and antigen processing; IFN-γ-induced genes are inhibited by prolonged LpqH stimulation | [115,116,117] | |
24-kDa lipoprotein (Rv1270c) | LprA | TLR2/1 | CD14/CD36 | Induces cytokine response and regulates antigen presenting cell functions | [117,119] | |
24-kDa lipoprotein (Rv1411c) | LprG | TLR2/1; TLR2 | CD14 | Long-term exposure of LprG inhibits the processing of MHC-II antigen; Short-term exposure of LprG induces the production of TNF-α | [117,118] | |
24-kDa lipoprotein (Rv1016c) | LpqT | TLR2 | Unknown | Induces TLR2-dependent apoptosis in macrophages and inhibits MHC expression and antigen processing | [120] | |
38-kDa glycolipoprotein | PhoS1 | TLR2/1, TLR4 | Unknown | Activates the ERK1/2 and p38 MAPK signaling, which in turn induces TNF-α and IL-6 expression | [117,121] | |
Lipoylated and glycosylated Mtb lipoprotein (Rv2873) | MPT83 | TLR2 | unknown | MPT83-induced cytokine production is decreased in TLR2 defective mice | [122] | |
Lipoglycans/Glycolipids | ||||||
Lipoarabinomannan | LAM | TLR2/1; TLR2 | CD14 | Mtb LAM induces the production of pro- and anti-inflammatory cytokines to activate neutrophils | [111,123] | |
Arabinosylated lipoarabinomannan | AraLAM | TLR2 | Unknown | Induces pro-inflammatory responses | [124] | |
Lipomannans | LM | TLR2/1; TLR2; | CD40/CD86 | Induces TNF-α and NO secretion to activate macrophages | [125,126] | |
phosphatidylinositol dimannoside | PIM2/6 | TLR2 | Unknown | Induces the expression of TNF-α to activate macrophages | [111,127] | |
Trehalose dimycolate | TDM | TLR2 | CD14/MARCO | Induces NF-κB signaling | [128] | |
Others | ||||||
Heat shock protein 70 | HSP70 | TLR2 | Unknown | Inhibits the secretion of IL-6 in TLR2-deficient macrophages | [129] | |
55-kDa flavin containing monooxygenase (Rv3083) | MymA | TLR2 | CD40/CD80/ CD86/HLA-DR | Upregulates the expression of TLR2 and its co-simulatory molecules Activates macrophages by inducing TNF- α and IL-12 | [130] | |
PE_PGRS proteins (Rv1818c) | PE_PGRS33 | TLR2 | CD14 | Contributes to Mtb entering macrophages by interacting with TLR2 | [131,132] | |
Secreted antigenic targets of 6-kDa (ESAT-6)family proteins (Rv1198) | EsxL | TLR2 | Unknown | Induces TNF-α and IL-6 through TLR2-dependent NF-κB and MAPK signaling | [133] | |
PE/PPE protein (Rv1196) | PPE18 | TLR2 | Unknown | Interacts with TLR2 to produce IL-10 and SOCS3 to in turn inhibit TLR2 signaling | [134,135] | |
PE/PPE protein (Rv1789) | PPE26 | TLR2 | CD80/CD86 | Activates macrophages by inducing pro-inflammatory cytokines TNF-α, IL-6, and IL-12 | [136] | |
PE/PPE protein (Rv1808) | PPE32 | TLR2 | Unknown | Induces both anti-inflammatory cytokine IL-10 and pro-inflammatory cytokines TNF-α and IL-6 | [137] | |
PE/PPE protein (Rv3425) | PPE57 | TLR2 | CD40/CD80/ CD86 | Activates macrophages by inducing pro-inflammatory cytokines TNF-α, IL-6, and IL-12 | [138] | |
Leucine-responsive regulatory protein | Lrp | TLR2 | Unknown | Inhibits LPS-induced pro-inflammatory cytokine IL-12 and TNF-α production | [139] | |
M. avium | Glycopeptidolipids | GPLs | TLR2, TLR4 | Unknown | Promotes the activation of macrophages dependent on TLR2 and MYD88 TLR2 recognition of GPLs is dependent on specific acetylation and methylation patterns | [140,141,142] |
M. abscessus | Glycopeptidolipids | GPLs | TLR2 | Unknown | The switch of Mab from the smooth to the rough morphotype depends on the presence of bacterial surface GPLs | [143] |
M. smegmatis | Phosphoinositol-capped LAM | PILAM | TLR2/ TLR1 | Unknown | High affinity binding to TLR2 and strong pro-inflammatory responses | [125,144] |
Arabinosylated lipoarabinomannan | AraLAM | TLR2 | CD14? | The lung inflammation induced by AraLAM is diminished in TLR2-deficient mice | [145] | |
Dimannoside hosphatidyl-myo-inositol mannosides | PIM2/6 | TLR2 | Unknown | Induces the expression of TNF to activate primary macrophages | [127] |
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Hu, W.; Spaink, H.P. The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target. Biology 2022, 11, 246. https://doi.org/10.3390/biology11020246
Hu W, Spaink HP. The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target. Biology. 2022; 11(2):246. https://doi.org/10.3390/biology11020246
Chicago/Turabian StyleHu, Wanbin, and Herman P. Spaink. 2022. "The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target" Biology 11, no. 2: 246. https://doi.org/10.3390/biology11020246