|Year : 2021 | Volume
| Issue : 2 | Page : 223
|Toll-like receptors in dermatology, venereology, and leprosy
Sneha Gandhi1, K Ravindra2
1 Department of Dermatology, Venereology and Leprosy, GIMS, Gulbarga, Karnataka, India
2 Department of Dermatology, Venereology and Leprosy, JJMMC, Davangere, Karnataka, India
|Date of Web Publication||16-Apr-2021|
GIMS, Gulbarga, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Toll-like receptors (TLRs) represent a family of Type I transmembrane proteins characterized by an extracellular leucine-rich repeat domain and a cytoplasmic domain. TLRs represent a conserved group of receptors which help the immune system to function properly. Different TLRs are associated with an array of skin diseases. TLR agonists and antagonists have great potential for the treatment of allergic and inflammatory diseases.
Keywords: Acne, atopic dermatitis, psoriasis, toll-like receptors
|How to cite this article:|
Gandhi S, Ravindra K. Toll-like receptors in dermatology, venereology, and leprosy. Indian J Dermatol 2021;66:223
| Introduction|| |
The immune system has two lines of defense: innate and adaptive immunity. Innate immunity is the first immunological, antigen-dependent nonspecific mechanism against a pathogen. Adaptive immunity, on the other hand, is antigen-dependent and antigen-specific; it has the capacity for memory, which enables the host to mount a more rapid and efficient immune response on subsequent exposure to the antigen.
In response to a pathogen exposure, a host employs both the innate and adaptive arms of the immune system to protect against infection. The innate immune response utilizes physical barriers such as skin and mucosal epithelium as a means of avoiding infection and rapid cellular responses enacted by dendritic cells (DCs), monocytes, natural killer cells, granulocytes, and epithelial cells to protect a newly infected host. These cells express pattern recognition receptors that mediate responses to pathogen-associated molecular patterns (PAMPs) that are conserved among microorganisms. Human toll like receptors (TLRs) are one such family of pattern recognition receptors that are capable of initiating innate immune responses and influencing subsequent adaptive immune responses.
TLRs represent a family of type I transmembrane proteins characterized by an extracellular leucine-rich repeat domain and a cytoplasmic domain, similar to interleukin-1 (IL-1) receptor.
The name “TLR” is derived from the structural and functional resemblance to a transmembrane receptor discovered in Drosophila melanogaster flies. Toll is a regulator for Drosophila embryonic development, responsible for the determination of the dorsoventral axis of the insect. The German word “Toll” (”fantastical” or “strange”) was used by the German research group which discovered that flies with mutant forms of this protein took on a severely distorted phenotype. In 1997, Medzhitov et al. described the first human homolog of the Drosophila toll receptor, which is now known as TLR4.
TLRs are transmembrane proteins with the extracellular portion composed of horseshoe-shaped leucine-rich repeats, whereas the intracellular portion shares homology with the cytoplasmic domain of the IL-1 receptor [Figure 1].
Effects of toll-like receptor activation
- TLR activation promotes phagocytosis of pathogens and inflammatory responses to phagosome contents as well as the maturation of phagosomes, allowing for the killing of phagocytosed bacteria
- TLR activation triggers antimicrobial pathways that promote the release of nonspecific antibacterial molecules such as antimicrobial peptides
- Furthermore, TLR activation facilitates and instructs the development of adaptive immune responses by increasing the levels of expression of co-stimulatory molecules such as CD80 and CD86 on dendritic cells, allowing dendritic cells to activate T-cells and release cytokines
- TLR activation may also lead to apoptosis.
Toll-like receptor expression in skin
It appears that keratinocytes in different layers of the epidermis may express different TLRs. As keratinocytes progress from the basal layer to the surface of the skin, their patterns of TLR expression may also change. Antibody staining of the biopsies demonstrated cytoplasmic TLR1 and TLR2 expression throughout the epidermis with TLR2 staining most strongly on basal keratinocytes. The basal layer also demonstrated TLR5 staining. Other studies report expression of TLR4 on keratinocytes. Antibody staining of skin sections demonstrated the presence of TLR2 and TLR4 throughout the epidermis [Table 1].
Role of TLR receptors in dermatology, venereology and leprosy
TLRs have been found to have a role in pathogenesis of several conditions [Table 2].
|Table 2: Applications of toll-like receptors in dermatology, venereology, and leprosy|
Click here to view
Role of toll-like receptors in psoriasis
Psoriasis is a chronic inflammatory skin disease mediated by T-cells and characterized clinically by hyperproliferation of the epidermis. It was noted that TLR2 appeared to be more strongly expressed in the upper epidermis of psoriasis patients. Whereas TLR2 was more strongly expressed in the basal layers of normal and nonlesional skin. Furthermore, TLR5 expression was reduced in basal keratinocytes of lesions as compared with normal skin. Another group of investigators found that the basal keratinocytes of psoriatic skin demonstrated a strong and diffuse expression of TLR1.
Role of toll-like receptors in leprosy
Patients with the tuberculoid form of the disease more strongly expressed TLR2 and TLR1 within the lesion as compared with patients with lepromatous leprosy, suggesting that lepromatous patients may not be as able to activate cellular immune responses. Thus, in leprosy, the activation and regulation of TLR2 and TLR1 at the site of disease may contribute to the host's defense against Mycobacterium leprae.
| Conclusion|| |
TLRs represent a conserved group of receptors which help the immune system to function properly. Different TLRs are associated with an array of skin diseases. TLR agonists and antagonists have great potential for the treatment of allergic and inflammatory diseases. More research must discern the relationship between specific TLRs and the corresponding disease to harness the therapeutic potential of TLR ligands. Although studies have proven that TLR agonists such as CpG can induce a robust immune response, the efficacy of the vaccines, optimization of dosage, long-term effects, and augmentation requires further study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]
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