What is a TLR antagonist?
TLR agonists have been developed to treat allergies, cancers, and chronic infections by upregulating the innate immune system. TLR antagonists may be used to treat a number of inflammatory conditions, such as rheumatoid arthritis and systemic lupus erythematosus.
Where is TLR3 located?
Although TLR3, 7 and 9 all reside in intracellular compartments, the mechanisms that dictate their location are different for each. The intracellular location of TLR3 is determined by a 23- amino acid sequence present in the linker region between transmembrane and TIR domain (20).
Where is TLR9 located?
the 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 TLR recognizes flagellin?
Among the PRRs, there is a family of Toll-like receptors (TLRs), including TLR5, that recognize a wide variety of PAMPs and elicit innate immune responses. TLR5 is known to specifically sense and recognize flagellin, the major structural protein of bacterial flagella.
What cells express TLR3?
TLR3 Expression in SLE In humans TLR3 is restricted to myeloid dendritic cells, but in mice TLR3 is also expressed on macrophages [25, 29]. TLR3 has been shown to be expressed in the kidney and on glomerular mesangial cells [17, 30, 31].
What is the role of TLR3?
TLR3 is a member of the toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLR3 recognizes double-stranded RNA, a form of genetic information carried by some viruses such as reoviruses.
What activates TLR9?
TLR9 is usually activated by unmethylated CpG sequences in DNA molecules. Once activated, TLR9 moves from the endoplasmic reticulum to the Golgi apparatus and lysosomes, where it interacts with MyD88, the primary protein in its signaling pathway.
Is TLR9 intracellular?
TLR3, TLR7 and TLR9 recognize nucleic acids and are localized to intracellular compartments where they normally respond to viral nucleic acids.
What are TLR9 agonists and antagonists 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).
Is there a toll-like receptor antagonism for Duchenne muscular dystrophy?
Toll-like Receptor Antagonism as a Novel Anti-inflammatory Treatment Approach for Duchenne Muscular Dystrophy Kanneboyina Nagaraju1, Louis Brenner2, Kathryn Haviland2, Sudhir Agrawal2 1Center for Genetic Medicine Research, Children’s National Medical Center, Washington, DC. 2Idera Pharmaceuticals, Cambridge, MA.
What is the role of TLR9 in heart disease?
TLR9 expression in hearts with pressure overload leads to increased inflammation due to damaged mitochondria and activation of the CpG binding site on TLR9. There is evidence that TLR9 may play a role in heart health for individuals who have already suffered a myocardial infarction.
Is TLR 7 over-expressed in Duchenne muscular dystrophy?
TLR 7 is significantly over-expressed in DMD muscle at all stages of the disease. MYD88 knockout led to improved skeletal and cardiac muscle function in ~1-year-old mdxmice. Treatment with a TLR antagonist candidate through 5 weeks reduced inflammation and improved disease-associated outcomes in mdxmice.