Table 3.
Human Studies Outcome Related to TLRs
| TLR Type | Target Tissue | Subjects | Evaluated | Evaluated Cytokines | Results | |
|---|---|---|---|---|---|---|
| Ahmad, et al (2012) 137 | TLR2 TLR4 |
• PBMC • AT |
OW/OB T2D |
MyD88, IRAK1, TRAF6 | IL-6, TNFα | • ↑ MyD88, IRAK1, TRAF6 gene expression in PBMC in OB & OW compared to lean • ↑ TLR2 & TLR4 gene expression in scAT in OB compared to lean and OW • ↑ MyD88 gene expression in scAT in OB |
| Reyna, et al (2008) 138 | TLR2 TLR4 |
Muscle | OB T2D |
IκBα NF-κB |
IL-6, TNFα, SOD2 | • ↑ TLR4, IL-6, TNFα, SOD2, IkBα gene expression & protein content |
| Creely, et al (2007)135 | TLR2 TLR4 |
Abdominal subcutaneous AT (scAT) |
OB T2D |
NF-κB MyD88 TRAF6 | IL-6, TNFα | • ↑ TLR2, MyD88, TRAF6 gene expression & protein content • ↑ IL-6 & TNFα expression following LPS stimulation • ↑ TNFα plasma levels |
| Arias-Loste, et al (2016) 139 | TLR2 TLR6 |
• PBMC • Liver biopsy |
OB NAFLD |
- | IL-6, TNFα, IL-1β | • ↑ TLR2/6 in PBMC in OB • ↑ TLR6 in liver cell • ↑ IL-6, TNFα, IL-1β upregulation in hepatocytes • ↑IL-6 secretion in PBMC following TLR2/6 stimulation • ↑ TNFα & IL-1β in PBMC in response to TLR2 provocation |
| Ahmad, et al (2015) 140 | TLR2 TLR4 |
ScAT | OW/OB T2D |
MyD88 IRAK1 | IL-6, TNFα, IL-18, | • ↑ IRAK1 gene expression & protein content & positive significant correlation with TLR2 & MyD88 gene expression • ↑ IL-6, TNFα & IL-18 plasma levels & positive significant correlation with IRAK1 gene expression |
| Gupta, et al (2017) 141 | TLR1-10 | • MONs • NEU |
OB T2D |
- | IL-10, IL-6, CRP, IL-8, TNFα, IFN-β, IL-8, IL-1β, IFN-γ, IL-12 |
• No difference in plasma level of all cytokine except IFN-β (poor glycemic control) • ↑ IFN-β, IL-6 gene expression in MONs and NEUs • ↑ TLR1,3,5,7–10 in MONs |
| Thomas, et al (2017)142 | TLR2 TLR10 |
ScAT | OW/OB T2D |
- | TNFα, IL-23, CXC10, CCL5, CCL2, CCR5, IL-12A |
• ↑ TLR10 gene expression that correlated with TLR2, TNFα, IL-23, CXC10, CCL5, CCL2, CCR5, IL-12A |
| Cuevas, et al (2017) 143 | TLR4 | • ScAT • VAT (surgery) |
OB MetS |
MyD88 PAI-1 |
IL-6, TNFα | • ↑ MyD88 gene expression in ScAT that correlated with TLR4 & PAI-1 • No significant trend in expression of TLR4, PAI-1, IL-6 |
| Amiri, et al (2018) 144 | TLR2 TLR4 |
PBMC | OB IR |
MyD88 NF-κB TRIF |
- | • ↑ TLR4 gene expression in OB with IR. • No change in gene expression of TLR2, MyD88, NF-κB & TRIF between IR & non-IR |
Note: Arrows indicate significance at P-values ≤0.05.
Abbreviations: TLR, toll-like receptor; PBMC, peripheral blood mononuclear cell; AT, adipose tissue; OW, overweight; OB, obese; MyD88, myeloid differentiation primary response 88; T2D, type 2 diabetes; IRAK1, interleukin-1 receptor-associated kinase 1; TRAF6, tumor necrosis factor receptor (TNFR)-associated factor 6; IL, interleukin; TNFα, tumor necrosis factor α; scAT, subcutaneous adipose tissue; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; SOD2, superoxide dismutase 2; LPS, lipopolysaccharide; NAFLD, non-alcoholic fatty liver diseases; MONs, monocytes; NEU, neutrophils; IFN, interferon; CCR, C-C chemokine receptor; PAI-1, plasminogen activator inhibitor-1; CCL, C-C chemokine ligand; CXCR, C-X-C chemokine receptor; VAT, visceral adipose tissue; IR, insulin resistance; TRIF, toll-interleukin-1 receptor domain-containing adapter protein inducing interferon β; non-IR, non-insulin resistance.