Signalling of Toll-Like Receptors

Abstract

Since Toll-like receptor (TLR) signaling was found crucial for the activation of innate and adaptive immunity, it has been the focus of immunological research. There are at least 13 identified mammalian TLRs, to date, that share similarities in their extracellular and intracellular domains. A vast number of ligands have been identified that are specifically recognized by different TLRs. As a response the TLRs dimerize and their signaling is initiated. The molecular basis of that signaling depends on the conserved part of their intracellular domain; namely the Toll/IL-1 receptor (TIR) domain. Upon TLR dimerization a TIR-TIR structure is formed that can recruit TIR-containing intracellular proteins that mediate their signaling. For this reason these proteins are named adapters. There are five adapters identified so far named myeloid differentiation primary response protein 88 (MyD88), MyD88-adapter like (Mal) or TIR domain-containing adapter (TIRAP), TIR domain-containing adapter inducing interferon-beta (IFN-beta) (TRIF) or TIR-containing adapter molecule-1 (TICAM-1), TRIF-related adapter molecule (TRAM) or TICAM-2, and sterile alpha and HEAT-Armadillo motifs (SARM). The first four play a fundamental role in TLR-signaling, defining which pathways will be activated, depending on which of these adapters will be recruited by each TLR. Among these adapter proteins MyD88 and TRIF are now considered as the signaling ones and hence the TLR pathways can be categorized as MyD88-dependent and TRIF-dependent.

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

“…Several TLR genes were found to be 1.5-to 3-fold upregulated in this study; these included TLR1, TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, TLR9, TLR10, out of which TLR7 was 3-fold upregulated. TLRs are generally grouped into two main groups based on the recognition of pathogen-associated molecular patterns (PAMPS) from invading agents: the first group comprises TLR1, TLR2, TLR4, and TLR6 and recognizes PAMPS from lipids; the second group consists of TLR3, TLR7, TLR8, and TLR9 that recognizes PAMPS from nucleic acids (Brikos and O'Neill 2008). TLR signaling leads to the activation of innate and adaptive immunity.…”

Human gene expression profiles of susceptibility and resistance in tuberculosis

“…Simultaneously, the data reveal an increased expression of several interferoninducible genes, including guanylate binding protein 1 and 2, interferon alpha-inducible protein 6 and 27, ISG15 ubiquitin-like modifier and 2 0 ,5 0 -oligoadenylate synthetase 1 (see Table 3), which might illustrate the induction of interferon responses upon activation of pattern recognition receptors pathways. 20,21 Intriguingly, a distinct gene expression profile between TB and LTBI was observed when analysing expression of well-defined subsets of macrophage-and NK cell-associated genes. Macrophage-associated genes were upregulated in TB Host gene expression profiles in tuberculosis J Maertzdorf et al patients, whereas NK cell-associated genes were downregulated in TB patients as compared with LTBI patients (Table 3, list of cell-type-associated genes in part derived from Gaucher et al 22 ).…”

Myocardial Ischemia/Reperfusion Injury Is Mediated by Leukocytic Toll-Like Receptor-2 and Reduced by Systemic Administration of a Novel Anti–Toll-Like Receptor-2 Antibody

“…12 On activation, TLRs exert their inflammatory response through nuclear factor-B (NF-B) translocation to the nucleus. 13 Therefore, inhibition of TLRs may provide new therapeutic options after MI. This view is supported by recent observations in TLR-knockout mice.…”