Toll-like receptor 2

Toll-like receptors (TLR) belong to the group of PRRs (Pattern Recognition Receptors), which are used for the recognition of so-called "Pathogen Associated Molecular Patterns" ( PAMPs ). TLRs are mostly found on or in pathogens and control the activation of certain genes. There are now 10 (TLR-1 to 10) and 12 murine (TLR-1 to 9 + 11 and 13) in humans. 6 of the human TLRs bind PAMPs extracellularly (TLR-1, 2, 4, 5, 6, 10) while 4 are only localized intracellularly (TLR-3, 7, 8 and 9).

TLRs are expressed by immune cells of the innate and also by cells of the adaptive immune system (B and T cells). This wide distribution makes TLRs an excellent tool for both the innate and the adaptive immune system. TLRs are thus responsible for the recognition of pathogens and the activation of antigen-specific acquired immunity. Through the activity of TLRs, the innate defence mechanisms (see below immunity, innate) can distinguish between "self" and "foreign".

TLR1 is a co-receptor for TLR2 and is located on the cell surface. The TLR1/TLR2 dimer recognizes MAPMs on the cell surface like tri-acetylated microbial lipoproteins (MAMP=microbial associated molecular pattern).

The Toll-like receptor TLR2 and various The Toll-like receptor TLR2 and various polymorphisms have important effects in various autoimmune diseases; the co-function of its dimer TLR1 is not always clear.

Patients with atopic eczema express TLR2 at a reduced level compared to healthy individuals. This correlation is associated with an increased transepidermal water loss (TEWL - barrier disorder of the epidermis). Therefore, it can be assumed that reduced epidermal TLR2 expression plays an important role in the pathogenesis of atopic eczema (Kuo IH et al. 2012).

TLR2 activity is not a mandatory requirement for tolerance development against oral allergens. However, oral TLR2 activation modulates humoral IgE and IgA responses in tolerance development to oral allergens.

Polymorphisms in the genes encoding TLR1, TLR2, TLR4, TLR6 lead to a number of diseases.

The expression of TLR2 is upregulated in lesional skin of patients with severe acne vulgaris. This may be attributed to the increased colonization by propionibacteria (Bakry OA et al. (2014).

Osteoblasts recognize bacterial pathogens via TLR2 receptors. Remarkably, the expression of TLR2 receptors is reduced by increased endothelin-1 levels. Endothelines are elevated in chronic systemic diseases such as congestive heart disease, diabetes mellitus and chronic renal failure. This constellation is associated with a poor prognosis for bone infections (Suzaki A et al. 2014).

The expression of TLR2 and TLR4 genes is correlated with serum lipid levels. An increase in serum lipids and a hyperlipidemic leads to an upregulation of these toll-like receptors (Zhu et al. 2015).

The TLR2-receptor is expressed in human HNSCC (=head and neck squamous cell carcinoma) carcinomas and seems to have a direct tumor activating function. Blocking antibodies TLR2-receptor antibodies reduce tumor growth. (Farnebo L et al. 2015).

In animal experiments, TLR-2 knock-out mice showed schizophrenia-like symptoms, such as hyperlocomotion and anxiolytic-like behavior.

In mice, TLR2 is expressed in neurons, glial cells and smooth muscle cells of the intestinal wall. TLR2-deficient mice show intestinal dysmotility and disturbances in the secretory function of the mucosa.

1. Bakry OA et al (2014) Toll-like receptor 2 and P. acnes: do they trigger initial acne vulgaris lesions? Anal Quantum Cytopathol Histpathol 36:100-110.
2. Brun P et al (2013) Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology 145:1323-1233.
3. Farnebo L et al (2015) Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell carcinoma. Oncotarget 6:9897-9907.
4. Kim CH et al(2014) Toll-like receptor 2 promotes bacterial clearance during the initial stage of pulmonary infection with Acinetobacter baumannii. Mol Med Rep 9:1410-1414.
5. Kim J (2005) Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology 211:193-198.
6. Kuo IH et al (2012) Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair. J Invest Dermatol 133:988-998.
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8. Park SJ et al.(2015) Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice. Sci Rep 5:8502.
9. Schurz H et al (2015) TLR1, 2, 4, 6 and 9 Variants Associated with Tuberculosis Susceptibility: A Systematic Review and Meta-Analysis. PLoS One 10:e0139711.
10. Suzaki A et al(2014) Suppression of osteoblast Toll-like receptor 2 signaling by endothelin-1 J Orthop Res 32:910-914.
11. Tunis MC et al.(2015) Toll-like receptor 2 activators modulate oral tolerance in mice. Clin Exp Allergy 45:1690-1702.
12. Zhu YJ et al (2015) Toll-like receptor-2 and -4 are associated with hyperlipidemia. Mol Med Rep 12:8241-8246.