Current views of toll-like receptor signaling pathways - PubMed (original) (raw)

Current views of toll-like receptor signaling pathways

Masahiro Yamamoto et al. Gastroenterol Res Pract. 2010.

Abstract

On microbial invasion, the host immediately evokes innate immune responses. Recent studies have demonstrated that Toll-like receptors (TLRs) play crucial roles in innate responses that lead not only to the clearance of pathogens but also to the efficient establishment of acquired immunity by directly detecting molecules from microbes. In terms of intracellular TLR-mediated signaling pathways, cytoplasmic adaptor molecules containing Toll/IL-1R (TIR) domains play important roles in inflammatory immune responses through the production of proinflammatory cytokines, nitric oxide, and type I interferon, and upregulation of costimulatory molecules. In this paper, we will describe our current understanding of the relationship between TLRs and their ligands derived from pathogens such as viruses, bacteria, fungi, and parasites. Moreover, we will review the historical and current literature to describe the mechanisms behind TLR-mediated activation of innate immune responses.

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Figures

Figure 1

Figure 1

Extracellular and intracellular TLRs. TLRs can be divided into extracellular and intracellular TLRs. TLR1, TLR2, TLR4, TLR5, TLR6, and TLR11 recognize their ligands on the cell surface. On the other hand, TLR3, TLR7, TLR8, and TLR9 are intracellularly localized.

Figure 2

Figure 2

TLR-mediated MyD88-dependent or TRIF-dependent pathways. TIR domain-containing adaptors MyD88, TIRAP, TRIF, and TRAM define TLR-mediated signaling. MyD88 and TIRAP are adaptors for the MyD88-dependent pathways, which mainly activate proinflammatory cytokine production. On the other hand, TRIF and TRAM are adaptors for IRF3 activation, resulting in production of type I IFN by TLR3- or TLR4-mediated TRIF-dependent pathways. In pDCs, TLR7/TLR9-mediated MyD88-dependent pathways induce IRF7 activation, leading to IFN_α_ production.

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