What is TLR9?
TLR9 is an important receptor expressed in immune system cells including dendritic cells, macrophages, natural killer cells, and other antigen presenting cells. TLR9 preferentially binds DNA present in bacteria and viruses, and triggers signaling cascades that lead to a pro-inflammatory cytokine response.
Where is TLR9 located?
ER
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 does TLR9 recognize?
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 a TLR9 agonist?
(1) Toll-like receptor 9 (TLR9) agonists stimulate innate and adaptive antitumor immune responses. TLR9 agonists induce secretion of interferon-α(IFN-α) from immature plasmacytoid dendritic cells (pDCs), which may activate natural killer (NK) cell lysis of tumor cells and release tumor antigens (Ags).
Does TLR9 detect methylated bacterial DNA?
While most TLRs recognize molecu- lar structures that are normally absent from the host molecule repertoire, such as bacterial lipopolysaccha- rides, TLR9 principally detects foreign DNA by the absence of a single methyl-group at the 5-carbon posi- tion on cytosine of CpG dinucleotides.
Why are they called toll-like receptors?
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. TLRs received their name from their similarity to the protein coded by the toll gene identified in Drosophila in 1985 by Christiane Nüsslein-Volhard and Eric Wieschaus.
What does a toll like receptor do?
Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen (1).
Are TLRs on all cells?
All Answers (3) Many non-immune cell types do express TLRs. Examples are epithelial cells, neurons, astrocytes, and fibroblasts. They do respond to their activation too. Toll-like receptors.
Can DNA stimulate TLR receptors?
Intracellular delivery of bacterial DNA increases stimulation of TLR-9.
What is the function of TLR9 in immune cells?
TLR9 is a receptor for bacterial unmethylated CpG-containing DNA and for host-derived denatured DNA from apoptotic cells [11,236,237,189]. TLR9 was first identified as a DNA sensing receptor expressed in professional innate immune cells such as DCs and macrophages.
How does Toll like receptor 9 ( TLR9 ) work?
Toll-like receptor 9 (TLR9) senses unmethylated CpG dinucleotides, a hallmark of microbial DNA, that can be mimicked by synthetic oligonucleotides containing CpG motifs (CpG ODNs).
How is TLR9 expressed in B and PDC cells?
In humans, TLR9 is almost exclusively expressed in B cells and PDC (Hornung et al., 2002), while in mice, TLR9 is expressed more widely including myeloid immune cells. In humans, TLR9 predominantly induces type IFN production in PDCs and polyclonal activation in B cells via MyD88/IRF7-dependent signaling.
What can TLR9 agonists and antagonists be used for?
TLR9 agonists and antagonists may be useful in treatment of a variety of inflammatory conditions, and research in this area is active. Autoimmune thyroid diseases have also been shown to correlate with an increase in expression of TLR9 on peripheral blood mononuclear cells (PBMCs).