Toll-like receptor 8 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''TLR8''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
TLR8 has also been designated as CD288 (
cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...
288). It is a member of the
toll-like receptor
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize ...
(TLR) family.
Function
TLR8 seems to function differently in humans and mice. Until recently, TLR8 was believed to be nonfunctional in mice, but it seems to counteract TLR7 activity
The TLR family plays a fundamental role in pathogen recognition and activation of
innate immunity
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
. TLRs are highly conserved from ''
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...
'' to
humans
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
and share structural and functional similarities. They recognize
pathogen-associated molecular patterns
Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. A vast arra ...
(PAMPs) that are expressed on
infectious agents
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
, and mediate the production of
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is predominantly expressed in lung and peripheral blood
leukocytes, and lies in close proximity to another family member,
TLR7, on chromosome X. Recent research has also shown the expression of TLR8 in hippocampal interneurons, with yet unknown function.
TLR8 can recognize GU-rich single-stranded RNA.
However, the presence of GU-rich sequences in the single-stranded RNA is not sufficient to stimulate TLR8.
TLR8 recognizes G-rich
oligonucleotide
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids ...
s.
TLR8 is an endosomal receptor that recognizes single stranded RNA (ssRNA), and can recognize ssRNA viruses such as Influenza, Sendai, and Coxsackie B viruses. TLR8 binding to the viral RNA recruits MyD88 and leads to activation of the transcription factor NF-κB and an antiviral response.
TLR8 recognizes single-stranded RNA of viruses such as HIV and HCV.
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]
Clinical significance
Genetic variants in TLR8 has recently been linked to susceptibility to pulmonary tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
.
As a drug target
* TLR8 agonists (e.g. VTX-2337
Motolimod (VTX-2337) is a drug which acts as a potent and selective agonist of toll-like receptor 8 (TLR8), a receptor involved in the regulation of the immune system. It is used to stimulate the immune system, and has potential application as an ...
) have undergone clinical trials as immune stimulants in combination therapy for some cancers.Immune Stimulant No Help When Added to Chemotherapy for Recurrent Ovarian Cancer. March 2017
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* TLR8 antagonists (e.g. CU-CPT9a
CU-CPT9a is a drug which acts as a potent and selective antagonist of Toll-like receptor 8 (TLR8), with an IC50 of 0.5nM. Activation of toll-like receptors triggers release of cytokines and other signalling factors, leading to inflammation. This ...
) may have therapeutic applications against autoimmune disorders.
References
Further reading
*
*
External links
*
PDBe-KB
provides an overview of all the structure information available in the PDB for Human Toll-like receptor 8 (TLR8)
8
Clusters of differentiation
{{gene-X-stub