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tel-00827710, version 1 - 29 May 2013
demonstrated that they are highly specific for their cognate ligand and, upon engagement,
different TLRs induce a variety of signaling pathways (Figure 5). While TLR3 and TLR4
signal through the adaptor molecule TRIF and trigger the production of type I IFN and
inflammatory cytokines, TLR1, 2, 4, 5 and 6 induce only inflammatory cytokines via
signaling through Myd88-dependent pathways (Kawai and Akira, 2010). TLR 7 and 9 also
signal via Myd88.
Figure 5. Signaling pathways downstream of TLRs. (A) Myd88-dependent pathway downstream of
TLR1/6, 2 and 4 and TRIF-dependent pathway activated by TLR3 and 4. (B) Myd88-dependent
pathway downstream of TLR7 and 9. Adapted from Takeuchi et al., 2010.
(ii) RIG-I-Like Receptors
The RIG-I-like receptors are critical for the detection of infecting viruses. Three cytoplasmic
receptors form this family. RIG-I, Mda5 and LPG2 are specific for viral RNA species (Table
2). RIG-I, in particular, detects short double-stranded RNAs only found during the replication
of RNA viruses, while Mda5 recognizes longer nucleic acid chains.
(iii) Nod-Like Receptors
The NOD-like receptor family consists of more than 20 unique members that are all cytosolic
(Table 2). Among them, NOD1 and NOD2 recognize the degradation products of bacterial
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