What is TLR9?

TLR9 is a receptor for bacterial unmethylated CpG-containing DNA and for host-derived denatured DNA from apoptotic cells [11,236,237,189].

What stimulates TLR9?

In mammals, 10 TLRs recognize conserved pathogen-associated molecular patterns, resulting in the induction of inflammatory innate immune responses. One of these, TLR9, is activated intracellularly by bacterial DNA and synthetic oligodeoxynucleotides (ODN), containing unmethylated CpG dinucleotides.

What does TLR9 detect?

TLR9 is activated in response to DNA, in particular DNA containing unmethylated CpG motifs that are more prevalent in microbial than mammalian DNA. By detecting foreign DNA signatures TLR9 can sense the presence of certain viruses or bacteria inside the cell and mount an immune response.

What is TLR9 ligand?

Toll-like receptor 9 (TLR9) recognizes specific unmethylated CpG motifs prevalent in microbial but not vertebrate genomic DNA leading to innate and acquired immune responses. Microbial DNA immunostimulatory effects can be mimicked by synthetic oligodeoxynucleotides containing these CpG motifs (CpG ODNs).

Where is TLR9?

TLR9 is located in the ER TLR9 localized to a reticular compartment that did not contain Rab5, an early endosome marker, Rab7 or Rab9, late endosome markers, Rab11, a recycling endosome marker, CD63, a lysosome marker, or a commercial Golgi marker (Figure 2 and data not shown).

What is TLR9 agonist?

Preclinically, TLR9 agonists are potent adjuvants of cancer vaccines with strong immunostimulatory effects. TLR9 agonists in combination with peptide vaccines increase antigen-specific T cells in multiple tumors including melanoma, NSCLC, breast cancer, and sarcoma.

How does TLR9 bind to DNA?

A recent structural study confirmed that TLR9 has a second DNA-binding site that binds to DNA containing cytosine at the second position from the 5′ end (5′-xCx DNA), which cooperatively promotes the dimerization and activation of TLR9 (Ohto et al., 2018).

Where is TLR9 found in cell?

TLR9 is retained intracellularly Although most TLRs are expressed at the cell surface, recent studies have shown that TLR9 is located in intracellular compartments.

Do T cells express TLR9?

However, certain TLRs are also expressed in T lymphocytes, and the respective ligands can directly modulate T cell function. TLR2, TLR3, TLR5 and TLR9 act as co-stimulatory receptors to enhance proliferation and/or cytokine production of T-cell receptor-stimulated T lymphocytes.

Where is CD40 expressed?

CD40 is constitutively expressed by antigen presenting cells, including dendritic cells, B cells and macrophages. It can also be expressed by endothelial cells, smooth muscle cells, fibroblasts and epithelial cells.

What does TLR3 recognize?

Endosomal Toll-like receptor 3 (TLR3) serves as a sensor of viral infection and sterile tissue necrosis. Although TLR3 recognizes double-stranded RNA, little is known about structural features of virus- or host-derived RNAs that activate TLR3 in infection/inflammatory states.

What is a DNA sensor?

DNA sensors are DNA-binding proteins that are component of the innate immune system which are capable of detecting perturbations in DNA homeostasis of the cell and activate the intracellular signaling cascades of the innate immune system as a response (67).

Do T cells express TLR4?

Toll-like receptors (TLRs) are critical components of innate immunity and function as rapid pathogen sensors. TLR4 is expressed on CD4+ T cells as well, the functional significance of which is unclear.

Which cell expresses CD40?

What is CD40 signaling?

CD40, a TNFR (Tumor Necrosis Factor Receptor) family member, conveys signals regulating diverse cellular responses, ranging from proliferation and differentiation to growth suppression and cell death.

What cells express TLR3?

TLR3 is localized to cell surfaces and endosomes in fibroblasts, macrophages, and some epithelial cell lines. In contrast, myeloid DCs only express TLR3 intracellularly. Immunofluoresence analysis has shown that endogenous TLR3 is localized to the early endosome, but not to late endosomes/lysosomes.

What is a TLR3 in teaching?

TLR3 payments are awarded for teachers who are taking on a time-limited school improvement project or one-off responsibility.

How does a DNA biosensor work?

Such analytical devices, known as biosensors, convert a biochemical reaction or interaction into an analytical signal that can be further amplified, processed and recorded. Among them, DNA biosensors consist of an immobilized DNA strand to detect the complimentary sequence by DNA–DNA hybridization.

What does sting pathway do?

The cGAS–STING pathway is a component of the innate immune system that functions to detect the presence of cytosolic DNA and, in response, trigger expression of inflammatory genes that can lead to senescence or to the activation of defense mechanisms. DNA is normally found in the nucleus of the cell.

Do T cells express TLR?

Abstract. Toll-like receptors (TLRs) are an essential part of the innate immune system. Their function on antigen presenting cells helps drive efficient T cell responses to pathogens. However, T cells also express several TLRs.