Toll-like receptor 8 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''TLR8''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
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 immunophe ...
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 protein, single-spanning receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophages ...
(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 immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...
. TLRs are highly conserved from ''
Drosophila
''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
'' to
humans
Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
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 produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
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 (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s, 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, Recombinant DNA, research, and Forensic DNA, forensics. Commonly made in the laboratory by Oligonucleotide synthesis, solid-phase ...
s.
TLR8 is activated by ssRNA and forms a dimer complex when uridine released from the degraded ssRNA binds at one active site in between the dimers and a short oligonucleotide binds to another active site on the surface of the TLR8 structure.
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 the myeloid differentiation primary response protein 88 (MyD88) and leads to activation of the transcription factor NF-κB and an antiviral response that leads to proinflammatory cytokine synthesis.
TLR8 recognizes single-stranded RNA of viruses such as HIV and HCV.
[ TLR8 is also involved in the activation of dendritic cells to produce inflammatory factors to help regulate tumor growth, so TLR8 is often used as a target in the research for therapies in treating cancers including ovarian cancer and lymphomas.]
Clinical significance
Genetic variants in TLR8 has recently been linked to susceptibility to pulmonary tuberculosis.
As a drug target
* TLR8 agonists (e.g. VTX-2337) have undergone clinical trials as immune stimulants in combination therapy for some cancers.
References
Further reading
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External links
*
PDBe-KB
provides an overview of all the structure information available in the PDB for Human Toll-like receptor 8 (TLR8)
{{TLR signaling pathway
8
Clusters of differentiation