TLR9

Toll-like receptor 9 is a is_associated_with::protein that in humans is encoded by the TLR9 is_associated_with::gene. TLR9 has also been designated as CD289 (is_associated_with::cluster of differentiation 289). It is a member of the is_associated_with::toll-like receptor (TLR) family.

Function
The TLR family plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are named for the high degree of conservation in structure and function seen between mammalian TLRs and the Drosophila transmembrane protein Toll. TLRs are transmembrane proteins, expressed on the cell surface and the endocytic compartment and recognize is_associated_with::pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents and initiate signalling to induce production of is_associated_with::cytokines necessary for the innate immunity and subsequent adaptive immunity. The various TLRs exhibit different patterns of expression. This gene is preferentially expressed in immune cell rich tissues, such as is_associated_with::spleen, is_associated_with::lymph node, is_associated_with::bone marrow and is_associated_with::peripheral blood leukocytes. Studies in mice and humans indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response.

TLR9 recognizes unmethylated CpG sequences in DNA molecules. CpG sites are relatively rare (~1%) on vertebrate genomes in comparison to bacterial genomes or viral DNA. TLR9 is expressed by numerous cells of the immune system such as is_associated_with::B lymphocytes, is_associated_with::monocytes, natural killer (NK) cells, and is_associated_with::plasmacytoid dendritic cells. TLR9 is expressed intracellularly, within the endosomal compartments and functions to alert the immune system of viral and bacterial infections by binding to DNA rich in CpG motifs. TLR9 signals leads to activation of the cells initiating pro-inflammatory reactions that result in the production of is_associated_with::cytokines such as type-I interferon and IL-12.

Clinical significance
There are new immunomodulatory treatments undergoing testing which involve the administration of artificial DNA oligonucleotides containing the CpG motif. CpG DNA has applications in treating allergies such as asthma, immunostimulation against cancer, immunostimulation against pathogens, and as is_associated_with::adjuvants in vaccines.

Protein interactions

 * TLR9 has been shown to interact with is_associated_with::RNF216.
 * It can be activated by is_associated_with::CpG Oligodeoxynucleotides such as is_associated_with::Agatolimod.