The Role of Toll-Like Receptors in Host Defenses
The Role of Toll-Like Receptors in Host Defenses
The family of toll-like receptors (TLRs) plays a central role in the cutaneous immune defense system. To date, different TLRs have been found on several major cell populations of the skin, such as keratinocytes, fibroblasts, antigen-presenting cells, and melanocytes.
Activation of TLRs leads, via different intracellular signaling pathways, to the production of proinflammatory stimuli, and is considered a danger signal that should transform the skin in to the functional state of defense. However, TLRs have also been implicated in tissue homeostasis and renewal.
Within the group of TLRs, two types have been identified: surface-expressed TLRs, which are predominantly active against bacterial cell wall compounds; and intracellular receptors, which preferentially recognize virus-associated pattern molecules. In addition, surface-expressed receptors trigger phagocytotic and maturation signals, while the intracellular TLRs lead to the induction of antiviral genes.
Our review aims to outline the importance of TLRs in the pathogenesis of numerous skin diseases and the potential of TLR agonists as a treatment option for various skin diseases.
The human skin presents the outer shield of the organism against potential external threats such as viruses, bacteria, and fungi. Besides the physical barrier, infections are also encountered by a rapid cellular response enacted by immune cells within the skin, which identify pathogen-associated molecular patterns within a foreign antigenic structure and induce a proinflammatory response. This central role of the immune defense system is carried out by the group of 'pathogen-associated pattern recognition receptors,' among which the group of tolllike receptors (TLRs) has evolved as the central family during the last years. Currently, 11 different TLRs are identified in humans of which ten have been found functional, all of which share similarities in their structure and function but respond to different microbial components (figure 1).
(Enlarge Image)
Figure 1.
Cellular localization and ligands for the family of toll-like receptors (TLRs). Whereas the surface-expressed TLRs are active against bacterial compounds, the intracellular receptors recognize virus-associated molecules. CpG= cytosine phosphatidyl guanosine; dsRNA= double-stranded RNA; LP = lipoprotein; LPS= lipopolysaccharides; LTA = lipoteichoic acid; MD-2 = lymphocyte antigen 96; PGN= peptidoglycan; ssRNA= single-stranded RNA.
Abstract and Introduction
Abstract
The family of toll-like receptors (TLRs) plays a central role in the cutaneous immune defense system. To date, different TLRs have been found on several major cell populations of the skin, such as keratinocytes, fibroblasts, antigen-presenting cells, and melanocytes.
Activation of TLRs leads, via different intracellular signaling pathways, to the production of proinflammatory stimuli, and is considered a danger signal that should transform the skin in to the functional state of defense. However, TLRs have also been implicated in tissue homeostasis and renewal.
Within the group of TLRs, two types have been identified: surface-expressed TLRs, which are predominantly active against bacterial cell wall compounds; and intracellular receptors, which preferentially recognize virus-associated pattern molecules. In addition, surface-expressed receptors trigger phagocytotic and maturation signals, while the intracellular TLRs lead to the induction of antiviral genes.
Our review aims to outline the importance of TLRs in the pathogenesis of numerous skin diseases and the potential of TLR agonists as a treatment option for various skin diseases.
Introduction
The human skin presents the outer shield of the organism against potential external threats such as viruses, bacteria, and fungi. Besides the physical barrier, infections are also encountered by a rapid cellular response enacted by immune cells within the skin, which identify pathogen-associated molecular patterns within a foreign antigenic structure and induce a proinflammatory response. This central role of the immune defense system is carried out by the group of 'pathogen-associated pattern recognition receptors,' among which the group of tolllike receptors (TLRs) has evolved as the central family during the last years. Currently, 11 different TLRs are identified in humans of which ten have been found functional, all of which share similarities in their structure and function but respond to different microbial components (figure 1).
(Enlarge Image)
Figure 1.
Cellular localization and ligands for the family of toll-like receptors (TLRs). Whereas the surface-expressed TLRs are active against bacterial compounds, the intracellular receptors recognize virus-associated molecules. CpG= cytosine phosphatidyl guanosine; dsRNA= double-stranded RNA; LP = lipoprotein; LPS= lipopolysaccharides; LTA = lipoteichoic acid; MD-2 = lymphocyte antigen 96; PGN= peptidoglycan; ssRNA= single-stranded RNA.
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