The Interleukin-1 Receptor/Toll-Like Receptor Superfamily: Signal Transduction During Inflammation and Host Defense

Dunne, Aisling; O’Neill, Luke A.J.

doi:10.1126/scisignal.1712003re3

Cited by 232 publications

(311 citation statements)

References 153 publications

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“…The TLR/IL-1R superfamily groups multiple receptors, which all play a crucial role in innate and adaptive immunity [13]. The TLR subfamily consists of 13 members that contain leucine-rich repeat motifs in their extracellular domain, which recognize distinct microbial patterns such as LPS, flagellin, viral doublestranded RNA and unmethylated CpG motifs.…”

Section: Il-1r and Tlr-4 Signaling To Nf-kbmentioning

confidence: 99%

TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme

Verstrepen

Bekaert

Chau

et al. 2008

Cell. Mol. Life Sci.

398

297

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Abstract. Toll-like receptors (TLRs) as well as the receptors for tumor necrosis factor (TNF-R) and interleukin-1 (IL-1R) play an important role in innate immunity by regulating the activity of distinct transcription factors such as nuclear factor-kB (NF-kB). TLR, IL-1R and TNF-R signaling to NF-kB converge on a common IkB kinase complex that phosphorylates the NF-kB inhibitory protein IkBa. However, upstream signaling components are in large part receptor-specific. Nevertheless, the principles of signaling are similar, involving the recruitment of specific adaptor proteins and the activation of kinase cascades in which protein-protein interactions are controlled by poly-ubiquitination. In this review, we will discuss our current knowledge of NF-kB signaling in response to TLR-4, TNF-R and IL-1R stimulation, with a special focus on the similarities and dissimilarities among these pathways.Keywords. Toll-like receptor 4, interleukin-1, tumor necrosis factor, NF-kB, signal transduction. NF-kB, does it still need to be introduced?Nuclear factor kB (NF-kB) is the generic name of a family of transcription factors that regulate the expression of a large number of genes involved in immune and inflammatory responses, as well as in cell survival, cell proliferation and cell differentiation. NFkB transcription factors are activated in response to various stimuli, including cytokines, infectious agents, injury and other stressful conditions requiring rapid reprogramming of gene expression. Inappropriate activation of the NF-kB signaling pathway is implicated in the pathogenesis of chronic inflammation and autoimmunity, certain hereditary disorders and various cancers. In mammals, the NF-kB family consists of five proteins sharing a highly conserved Rel homology domain: c-Rel, RelB, p65 (= RelA), p105 (= NF-kB1) and p100 (=NF-kB2). The first three contain Cterminal transactivation domains, while the others share a long C-terminal domain with multiple copies of ankyrin repeats, which inhibit their activation.

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Section: Il-1r and Tlr-4 Signaling To Nf-kbmentioning

confidence: 99%

TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme

Verstrepen

Bekaert

Chau

et al. 2008

Cell. Mol. Life Sci.

398

297

View full text Add to dashboard Cite

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“…17 Although bacteria trigger host responses by multiple mechanisms, the cornerstone of innate signalling is mediated by TLRs, a set of 10 well conserved pattern recognition receptors (PRR). [18][19][20] TLRs are transmembrane proteins characterized by an extracellular domain containing leucine-rich repeats and an intracellular domain homologous to the interleukin (IL)-1R, or Toll/IL-1R (TIR). Ligand-specific binding to TLR promotes interaction of the cytoplasmic TIR domain with adaptor proteins followed by the recruitment of multiple kinases and activation of downstream target effector systems, including the mitogenactivated kinases (MAPK) as well as the IjB/NF-jB transcriptional system.…”

Section: Discussionmentioning

confidence: 99%

Innate mechanisms for Bifidobacterium lactis to activate transient pro‐inflammatory host responses in intestinal epithelial cells after the colonization of germ‐free rats

et al. 2005

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“…However, individual TLRs can also induce specific programs in cells of the innate immune system that are tailored for the particular pathogen (12)(13)(14). TLRs bear homology to the IL-1R type 1 (IL-1RI) and share a similar signaling cascade culminating in activation of NF-B and mitogen-activated protein kinases (15,16). This process facilitates the transcription of genes regulating the inflammatory and adaptive immune responses.…”

mentioning

confidence: 99%

The Contribution of the Toll-Like/IL-1 Receptor Superfamily to Innate and Adaptive Immunity to Fungal Pathogens In Vivo

Bellocchio

Montagnoli

Bozza

et al. 2004

The Journal of Immunology

465

491

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In vitro studies have indicated the importance of Toll-like receptor (TLR) signaling in response to the fungal pathogens Candida albicans and Aspergillus fumigatus. However, the functional consequences of the complex interplay between fungal morphogenesis and TLR signaling in vivo remain largely undefined. In this study we evaluate the impact of the IL-1R/TLR/myeloid differentiation primary response gene 88 (MyD88)-dependent signaling pathway on the innate and adaptive Th immunities to C. albicans and A. fumigatus in vivo. It was found that 1) the MyD88-dependent pathway is required for resistance to both fungi; 2) the involvement of the MyD88 adapter may occur through signaling by distinct members of the IL-1R/TLR superfamily, including IL-1R, TLR2, TLR4, and TLR9, with the proportional role of the individual receptors varying depending on fungal species, fungal morphotypes, and route of infection; 3) individual TLRs and IL-1R activate specialized antifungal effector functions on neutrophils, which correlates with susceptibility to infection; and 4) MyD88-dependent signaling on dendritic cells is crucial for priming antifungal Th1 responses. Thus, the finding that the innate and adaptive immunities to C. albicans and A. fumigatus require the coordinated action of distinct members of the IL-1R/TLR superfamily acting through MyD88 makes TLR manipulation amenable to the induction of host resistance to fungi.

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The Interleukin-1 Receptor/Toll-Like Receptor Superfamily: Signal Transduction During Inflammation and Host Defense

Cited by 232 publications

References 153 publications

TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme

TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme

Innate mechanisms for Bifidobacterium lactis to activate transient pro‐inflammatory host responses in intestinal epithelial cells after the colonization of germ‐free rats

The Contribution of the Toll-Like/IL-1 Receptor Superfamily to Innate and Adaptive Immunity to Fungal Pathogens In Vivo

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