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, respo ...
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 ba ...
.
TLR8 has also been designated as CD288 (
cluster of differentiation 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 Bitopic protein, single-pass membrane-spanning Receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophage ...
(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. 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 species ...
'' 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 (PAMPs) that are expressed on
infectious agents, 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
leukocyte
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
s, and lies in close proximity to another family member,
TLR7
Toll-like receptor 7, also known as TLR7, is a protein that in humans is encoded by the ''TLR7'' gene. Orthologs are found in mammals and birds. It is a member of the toll-like receptor (TLR) family and detects single stranded RNA.
Function
T ...
, 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
oligonucleotides.
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.
[
]
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 w ...
.
As a drug target
* TLR8 agonists (e.g. VTX-2337) 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
/ref>
* TLR8 antagonists (e.g. CU-CPT9a) 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