Definition: Toll-like receptors (TLRs) are homologous to a Drosophila protein called Toll. 10 mammalian TLRs have been identified in 2005.

Toll-like receptors (TLRs) have an important role in innate immunity in mammals by recognizing conserved microbial components that are known as pathogen-associated molecular patterns (PAMPs).

Although the majority of these receptors sense pathogen components on the cell surface, a subset of them (TLR3, TLR7, TLR8 and TLR9) senses viral and bacterial nucleic acids in endosomal compartments.

Of considerable interest is the recent finding that TLR7 and TLR8 can also recognize small interfering RNA (siRNA), which is the main effector in RNA interference. This immune activation by siRNAs can be abrogated by the 2'-ribose modification of uridines.

 TLRs function to activate leukocytes in response to different types and components of microbes.

 TLRs appear to be required for responses to different classes of infectious pathogens.

 Different TLRs play essential roles in cellular responses to bacterial lipopolysaccharide (LPS, or endotoxin), other bacterial proteoglycans, and unmethylated CpG nucleotides, all of which are found only in bacteria, as well as double-stranded RNA, which is produced only by some viruses.

 TLRs function by receptor-associated kinases to stimulate the production of microbicidal substances and cytokines in the leukocytes.

Members

TLR1

TLR2

TLR3

TLR4

TLR5

TLR6

TLR7

TLR8

TLR9

TLR10

See also

 TLR signaling pathways

• TLR signaling pathway diseases

References

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 Puel A, Yang K, Ku CL, von Bernuth H, Bustamante J, Santos OF, Lawrence T, Chang HH, Al-Mousa H, Picard C, Casanova JL. Heritable defects of the human TLR signalling pathways. J Endotoxin Res. 2005;11(4):220-4. PMID: #16176658#

 Brunn GJ, Platt JL. The etiology of sepsis: turned inside out. Trends Mol Med. 2005 Nov 17; PMID: #16298551#

 Guerau-de-Arellano M, Huber BT. Chemokines and Toll-like receptors in Lyme disease pathogenesis. Trends Mol Med. 2005 Mar;11(3):114-20. PMID: #15760769#

 Netea MG, Van der Meer JW, Kullberg BJ. Toll-like receptors as an escape mechanism from the host defense. Trends Microbiol. 2004 Nov;12(11):484-488. PMID: #15488388#

 Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004 Oct;5(10):987-95. PMID: #15454922#

 Cook DN, Pisetsky DS, Schwartz DA. Toll-like receptors in the pathogenesis of human disease. Nat Immunol. 2004 Oct;5(10):975-9. PMID: #15454920#

 Clevers H. At the crossroads of inflammation and cancer. Cell. 2004 Sep 17;118(6):671-4. PMID: #15369667#

 Goldstein DR. Toll-like receptors and other links between innate and acquired alloimmunity. Curr Opin Immunol. 2004 Oct;16(5):538-44. PMID: #15341996#

 Kaisho T, Akira S. Regulation of dendritic cell function through toll-like receptors. Curr Mol Med. 2003 Dec;3(8):759-71. PMID: #14682496#