Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA

By G. Barton, Jonathan C. Kagan, R. Medzhitov. Nature Immunology, 2006

722 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/92170695db976ff5a631481e72069d1be7ce0ed2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Microbiology

Citations in the corpus

Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists (2007, positive): “Microbial and mammalian DNA and RNA have distinct base modifications that permit a degree of differential recognition by TLR; however, the intracellular localization of these receptors is essentia”
Type I interferons in host defense. (2006, positive): “Because there is little structural basis for discrimination between viral and host nucleic acids, it appears that pattern recognition in this case is aided by the compartmentalization of antiviral sensors and by activities of host nucleases that help eliminate self nucleic acids from the extracellul”
TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β (2008, background): “Studies have identified a notable aspect of TLR biology: a link between receptor localization, the type of transcriptional response induced and the class of microbe detecte”
TLR3: interferon induction by double-stranded RNA including poly(I:C). (2008, background): “In addition, the second type of DC precursor cell, pre-DC2 (previously known as plasmacytoid DC precursor), which expresses TLR7 and TLR9 and secretes large amounts of IFN-α in response to ssRNA and imidazoquinoline compounds (TLR7 ligands) or CpG DNA (TLR9 ligand), does not express TLR3 [30,31].”
A cell biological view of Toll-like receptor function: regulation through compartmentalization (2009, background): “The carbohydrates on the mature TLR9 protein lack the modifications that are typically acquired during transit through the Golgi, and microscopy studies have suggested that TLR9 rapidly translocates from the ER to endolysosomes in stimulated cell”
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses (2009, background): “It is interesting that recognition of viral DNA is dependent on the endosomal location of TLR9, suggesting that virion degradation in this compartment may be required for DNA to become accessible to TLR9 (30).”
Toll-like receptor function and signaling. (2006, background): “If manipulated to express on the plasma membrane, TLR9 can be stimulated by self DNA.(29) Thus endosomal expression of TLR7/9 can prevent self DNA from being recognized, although it is beneficial for recognizing viral DNA.”
NF-κB and the immune response (2006, background): “A recent report indicated that the intracellular, endosomal restriction of TLR9 is critical for discriminating between self and nonself DNA, as host DNA, unlike microbial DNA, does not usually enter the endosomal compartment (Barton et al., 2006).”
Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics (2022, background): “aeruginosa unmethylated bacterial CpG DNA intracellularly.(285) Interestingly, TLR9 is also activated by P.”
Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 (2009, background): “However, more recently, it has become clear that this discrimination is mainly achieved by the intracellular localization of these TLRs, which allows recognition of viral nucleic acids released into endosomal compartments by the endocytosed virus (Barton et al., 2006).”