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

Sci. STKE, 25 February 2003
Vol. 2003, Issue 171, p. re3
DOI: 10.1126/stke.2003.171.re3

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

  1. Aisling Dunne and
  2. Luke A. J. O'Neill*
  1. Department of Biochemistry and Biotechnology Institute, Trinity College, Dublin, Ireland.
  1. *Corresponding author. E-mail: laoneill{at}tcd.ie

Abstract

The signal transduction pathways activated by the proinflammatory cytokine interleukin-1 (IL-1) have been the focus of much attention because of the important role that IL-1 plays in inflammatory diseases. A number of proteins have been described that participate in the post-receptor activation of the transcription factor nuclear factor κB (NF-κB), and stress-activated protein kinases such as p38 mitogen-activated protein kinase (MAPK). It has also emerged that the type I IL-1 receptor (IL-1RI) is a member of an expanding receptor superfamily. These related receptors all have sequence similarity in their cytosolic regions. The family includes the Drosophila melanogaster protein Toll, the IL-18 receptor (IL-18R), and 10 Toll-like receptors (TLRs), TLR-1 to TLR-10, which bind to microbial products, activating host defense responses. Because of the similarity of IL-1RI to Toll, the conserved sequence in the cytosolic region of these proteins has been termed the Toll-IL-1 receptor (TIR) domain. The same proteins activated during signaling by IL-1RI also participate in signaling by other receptors with TIR domains. The receptor superfamily is evolutionarily conserved; members also occur in plants and insects, where they also function in host defense. The signaling proteins that are activated are also conserved across species. Differences are, however, starting to emerge in signaling pathways activated by different receptors. This receptor superfamily, therefore, represents an ancient signaling system that is a critical determinant of the innate immune and inflammatory responses.

Citation:

A. Dunne and L. A. O'Neill, The Interleukin-1 Receptor/Toll-Like Receptor Superfamily: Signal Transduction During Inflammation and Host Defense. Sci. STKE 2003, re3 (2003).

Activation of the Transcription Factor Nuclear Factor-Kappa B in Uterine Luminal Epithelial Cells by Interleukin 1 Beta 2: A Novel Interleukin 1 Expressed by the Elongating Pig Conceptus
D. J. Mathew, E. M. Newsom, J. M. Guyton, C. K. Tuggle, R. D. Geisert, and M. C. Lucy
Biol. Reprod. 92, 107-107 (1 April 2015)

Toll-Like Receptor Expression in the Blood and Brain of Patients and a Mouse Model of Parkinson's Disease
J. Drouin-Ouellet, I. St-Amour, M. Saint-Pierre, J. Lamontagne-Proulx, J. Kriz, R. A. Barker, and F. Cicchetti
Int J Neuropsychopharmacol 18, pyu103-pyu103 (1 April 2015)

The inflammasome adaptor ASC contributes to multiple innate immune processes in the resolution of otitis media
A. Kurabi, J. Lee, C. Wong, K. Pak, H. M. Hoffman, A. F. Ryan, and S. I. Wasserman
Innate Immunity 21, 203-214 (1 February 2015)

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant
A. U. Bielinska, P. E. Makidon, K. W. Janczak, L. P. Blanco, B. Swanson, D. M. Smith, T. Pham, Z. Szabo, J. F. Kukowska-Latallo, J. R. Baker et al.
J. Immunol. 192, 2722-2733 (15 March 2014)

The TNF Family Member 4-1BBL Sustains Inflammation by Interacting with TLR Signaling Components During Late-Phase Activation
J. Ma, B.-R. Bang, J. Lu, S.-Y. Eun, M. Otsuka, M. Croft, P. Tobias, J. Han, O. Takeuchi, S. Akira et al.
Sci Signal 6, ra87-ra87 (1 October 2013)

Structural insights into the interaction of IL-33 with its receptors
X. Liu, M. Hammel, Y. He, J. A. Tainer, U.-S. Jeng, L. Zhang, S. Wang, and X. Wang
Proc. Natl. Acad. Sci. USA 110, 14918-14923 (10 September 2013)

IL-1{beta}-specific recruitment of GCN5 histone acetyltransferase induces the release of PAF1 from chromatin for the de-repression of inflammatory response genes
N. Kim, H.-Y. Sun, M.-Y. Youn, and J.-Y. Yoo
Nucleic Acids Res 41, 4495-4506 (1 April 2013)

The E3 ubiquitin ligase MARCH8 negatively regulates IL-1{beta}-induced NF-{kappa}B activation by targeting the IL1RAP coreceptor for ubiquitination and degradation
R. Chen, M. Li, Y. Zhang, Q. Zhou, and H.-B. Shu
Proc. Natl. Acad. Sci. USA 109, 14128-14133 (28 August 2012)

Ubiquitin-specific Protease 4 Mitigates Toll-like/Interleukin-1 Receptor Signaling and Regulates Innate Immune Activation
F. Zhou, X. Zhang, H. van Dam, P. ten Dijke, H. Huang, and L. Zhang
J Biol Chem 287, 11002-11010 (30 March 2012)

Analysis of NLRP3 in the Development of Allergic Airway Disease in Mice
I. C. Allen, C. M. Jania, J. E. Wilson, E. M. Tekeppe, X. Hua, W. J. Brickey, M. Kwan, B. H. Koller, S. L. Tilley, J. P.- Y. Ting et al.
J. Immunol. 188, 2884-2893 (15 March 2012)

Glucocorticoids inhibit dendritic cell maturation induced by Toll-like receptor 7 and Toll-like receptor 8
A. Larange, D. Antonios, M. Pallardy, and S. Kerdine-Romer
J. Leukoc. Biol. 91, 105-117 (1 January 2012)

The Role of Intermediary Domain of MyD88 in Cell Activation and Therapeutic Inhibition of TLRs
M. Avbelj, S. Horvat, and R. Jerala
J. Immunol. 187, 2394-2404 (1 September 2011)

Differential Role of Toll-Interleukin 1 Receptor Domain-Containing Adaptor Protein in Toll-Like Receptor 2-Mediated Regulation of Gene Expression of Hepatic Cytokines and Drug-Metabolizing Enzymes
R. Ghose, T. Guo, J. G. Vallejo, and A. Gandhi
Drug Metab. Dispos. 39, 874-881 (1 May 2011)

Direct Inhibition of Human RANK+ Osteoclast Precursors Identifies a Homeostatic Function of IL-1{beta}
B. Lee, T.-H. Kim, J.-B. Jun, D.-H. Yoo, J.-H. Woo, S. J. Choi, Y. H. Lee, G. G. Song, J. Sohn, K.-H. Park-Min et al.
J. Immunol. 185, 5926-5934 (15 November 2010)

Viral Inhibitory Peptide of TLR4, a Peptide Derived from Vaccinia Protein A46, Specifically Inhibits TLR4 by Directly Targeting MyD88 Adaptor-Like and TRIF-Related Adaptor Molecule
T. Lysakova-Devine, B. Keogh, B. Harrington, K. Nagpal, A. Halle, D. T. Golenbock, T. Monie, and A. G. Bowie
J. Immunol. 185, 4261-4271 (1 October 2010)

MyD88-dependent TLR4 signaling is selectively impaired in alveolar macrophages from asymptomatic HIV+ persons
S. D. Tachado, X. Li, M. Bole, K. Swan, A. Anandaiah, N. R. Patel, and H. Koziel
Blood 115, 3606-3615 (29 April 2010)

Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation
S. Radtke, S. Wuller, X.-p. Yang, B. E. Lippok, B. Mutze, C. Mais, H. S.-V. de Leur, J. G. Bode, M. Gaestel, P. C. Heinrich et al.
J. Cell Sci. 123, 947-959 (15 March 2010)

Lysine 63-linked Polyubiquitination of TAK1 at Lysine 158 Is Required for Tumor Necrosis Factor {alpha}- and Interleukin-1{beta}-induced IKK/NF-{kappa}B and JNK/AP-1 Activation
Y. Fan, Y. Yu, Y. Shi, W. Sun, M. Xie, N. Ge, R. Mao, A. Chang, G. Xu, M. D. Schneider et al.
J Biol Chem 285, 5347-5360 (19 February 2010)

MSK1 regulates the transcription of IL-1ra in response to TLR activation in macrophages
J. Darragh, O. Ananieva, A. Courtney, S. Elcombe, and J. S. C. Arthur
Biochem. J. 425, 595-602 (1 February 2010)

Adjuvant Effects for Oral Immunization Provided by Recombinant Lactobacillus casei Secreting Biologically Active Murine Interleukin-1{beta}
A. Kajikawa, K. Masuda, M. Katoh, and S. Igimi
CVI 17, 43-48 (1 January 2010)

Tumor Progression Locus 2 (Map3k8) Is Critical for Host Defense against Listeria monocytogenes and IL-1{beta} Production
L. A. Mielke, K. L. Elkins, L. Wei, R. Starr, P. N. Tsichlis, J. J. O''Shea, and W. T. Watford
J. Immunol. 183, 7984-7993 (15 December 2009)

Lipid Rafts and Caveolin-1 Coordinate Interleukin-1{beta} (IL-1{beta})-dependent Activation of NF{kappa}B by Controlling Endocytosis of Nox2 and IL-1{beta} Receptor 1 from the Plasma Membrane
F. D. Oakley, R. L. Smith, and J. F. Engelhardt
J Biol Chem 284, 33255-33264 (27 November 2009)

Interleukin-1{alpha} stimulates proinflammatory cytokine expression in human cardiac myofibroblasts
N. A. Turner, A. Das, P. Warburton, D. J. O''Regan, S. G. Ball, and K. E. Porter
Am. J. Physiol. Heart Circ. Physiol. 297, H1117-H1127 (1 September 2009)

Protein-tyrosine Phosphatase-{alpha} and Src Functionally Link Focal Adhesions to the Endoplasmic Reticulum to Mediate Interleukin-1-induced Ca2+ Signaling
Q. Wang, D. Rajshankar, D. R. Branch, K. A. Siminovitch, M. T. H. Abreu, G. P. Downey, and C. A. McCulloch
J Biol Chem 284, 20763-20772 (31 July 2009)

Activated macrophages induce hepcidin expression in HuH7 hepatoma cells
P. Matak, T. B. Chaston, B. Chung, S. K. Srai, A. T. McKie, and P. A. Sharp
haematol 94, 773-780 (1 June 2009)

Signals Through Glycoprotein 130 Regulate the Endothelial Differentiation of Cardiac Stem Cells
T. Mohri, Y. Fujio, M. Obana, T. Iwakura, K. Matsuda, M. Maeda, and J. Azuma
Arterioscler. Thromb. Vasc. Bio. 29, 754-760 (1 May 2009)

TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation
A. Larange, D. Antonios, M. Pallardy, and S. Kerdine-Romer
J. Leukoc. Biol. 85, 673-683 (1 April 2009)

GCK is essential to systemic inflammation and pattern recognition receptor signaling to JNK and p38
J. Zhong, L. C. Gavrilescu, A. Molnar, L. Murray, S. Garafalo, J. H. Kehrl, A. R. Simon, R. A. Van Etten, and J. M. Kyriakis
Proc. Natl. Acad. Sci. USA 106, 4372-4377 (17 March 2009)

Modulation of TLR Signaling by Multiple MyD88-Interacting Partners Including Leucine-Rich Repeat Fli-I-Interacting Proteins
P. Dai, S. Y. Jeong, Y. Yu, T. Leng, W. Wu, L. Xie, and X. Chen
J. Immunol. 182, 3450-3460 (15 March 2009)

Live Borrelia burgdorferi Spirochetes Elicit Inflammatory Mediators from Human Monocytes via the Toll-Like Receptor Signaling Pathway
V. A. Dennis, S. Dixit, S. M. O''Brien, X. Alvarez, B. Pahar, and M. T. Philipp
Infect. Immun. 77, 1238-1245 (1 March 2009)

Inflammatory Cytokines IL-1{beta} and TNF-{alpha} Regulate p75NTR Expression in CNS Neurons and Astrocytes by Distinct Cell-Type-Specific Signalling Mechanisms
S. Choi, and W. J. Friedman
ASN Neuro 1, AN20090009-AN20090009 (1 March 2009)

Roles of Caspase 1 and Extracellular Signal-Regulated Kinase in Inflammation-Induced Inhibition of Lacrimal Gland Protein Secretion
D. Zoukhri, S. Ko, P. C. Stark, and C. L. Kublin
IOVS 49, 4392-4398 (1 October 2008)

Alterations in MicroRNA Expression Contribute to Fatty Acid-Induced Pancreatic {beta}-Cell Dysfunction
P. Lovis, E. Roggli, D. R. Laybutt, S. Gattesco, J.-Y. Yang, C. Widmann, A. Abderrahmani, and R. Regazzi
Diabetes 57, 2728-2736 (1 October 2008)

Stimulation of Toll-like receptor 3 and 4 induces interleukin-1{beta} maturation by caspase-8
J. Maelfait, E. Vercammen, S. Janssens, P. Schotte, M. Haegman, S. Magez, and R. Beyaert
JEM 205, 1967-1973 (1 September 2008)

Mechanism of IL-1{beta}-Induced Increase in Intestinal Epithelial Tight Junction Permeability
R. Al-Sadi, D. Ye, K. Dokladny, and T. Y. Ma
J. Immunol. 180, 5653-5661 (15 April 2008)

Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-{kappa}B activation
H. Iha, J.-M. Peloponese, L. Verstrepen, G. Zapart, F. Ikeda, C. D. Smith, M. F. Starost, V. Yedavalli, K. Heyninck, I. Dikic et al.
EMBO J. 27, 629-641 (20 February 2008)

Mechanisms of Dexamethasone-Mediated Inhibition of Toll-Like Receptor Signaling Induced by Neisseria meningitidis and Streptococcus pneumoniae
T. H. Mogensen, R. S. Berg, S. R. Paludan, and L. Ostergaard
Infect. Immun. 76, 189-197 (1 January 2008)

Sensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3
E. Vercammen, J. Staal, and R. Beyaert
Clin. Microbiol. Rev. 21, 13-25 (1 January 2008)

IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex
A. A. Chackerian, E. R. Oldham, E. E. Murphy, J. Schmitz, S. Pflanz, and R. A. Kastelein
J. Immunol. 179, 2551-2555 (15 August 2007)

The LIM Protein, LIMD1, Regulates AP-1 Activation through an Interaction with TRAF6 to Influence Osteoclast Development
Y. Feng, H. Zhao, H. F. Luderer, H. Epple, R. Faccio, F. P. Ross, S. L. Teitelbaum, and G. D. Longmore
J Biol Chem 282, 39-48 (5 January 2007)

Human Hepatitis B Viral e Antigen Interacts with Cellular Interleukin-1 Receptor Accessory Protein and Triggers Interleukin-1 Response
C.-Y. Yang, T.-H. Kuo, and L.-P. Ting
J Biol Chem 281, 34525-34536 (10 November 2006)

Gonococcal Lipooligosaccharide Suppresses HIV Infection in Human Primary Macrophages through Induction of Innate Immunity
X. Liu, A. Mosoian, T. Li-Yun Chang, B. Zerhouni-Layachi, A. Snyder, G. A. Jarvis, and M. E. Klotman
The Journal of Infectious Disease 194, 751-759 (15 September 2006)

Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response through Toll-like receptors 2, 4, and 9 in species-specific patterns
T. H. Mogensen, S. R. Paludan, M. Kilian, and L. Ostergaard
J. Leukoc. Biol. 80, 267-277 (1 August 2006)

The myristoylation of TRIF-related adaptor molecule is essential for Toll-like receptor 4 signal transduction
D. C. Rowe, A. F. McGettrick, E. Latz, B. G. Monks, N. J. Gay, M. Yamamoto, S. Akira, L. A. O'Neill, K. A. Fitzgerald, D. T. Golenbock et al.
Proc. Natl. Acad. Sci. USA 103, 6299-6304 (18 April 2006)

Identification and Characterization of a Novel Bacterial Virulence Factor That Shares Homology with Mammalian Toll/Interleukin-1 Receptor Family Proteins
R. M. Newman, P. Salunkhe, A. Godzik, and J. C. Reed
Infect. Immun. 74, 594-601 (1 January 2006)

The Tumor Suppressor Cylindromatosis (CYLD) Acts as a Negative Regulator for Toll-like Receptor 2 Signaling via Negative Cross-talk with TRAF6 and TRAF7
H. Yoshida, H. Jono, H. Kai, and J.-D. Li
J Biol Chem 280, 41111-41121 (9 December 2005)

LPS induces CD40 gene expression through the activation of NF-{kappa}B and STAT-1{alpha} in macrophages and microglia
H. Qin, C. A. Wilson, S. J. Lee, X. Zhao, and E. N. Benveniste
Blood 106, 3114-3122 (1 November 2005)

Bruton's Tyrosine Kinase Is Involved in p65-mediated Transactivation and Phosphorylation of p65 on Serine 536 during NF{kappa}B Activation by Lipopolysaccharide
S. L. Doyle, C. A. Jefferies, and L. A. O'Neill
J Biol Chem 280, 23496-23501 (24 June 2005)

Differential regulation of virus-specific T-cell effector functions following activation by peptide or innate cytokines
C. Beadling, and M. K. Slifka
Blood 105, 1179-1186 (1 February 2005)

Cell Signaling and the Genesis of Neuropathic Pain
R.-R. Ji, and G. Strichartz
Sci Signal 2004, re14-re14 (28 September 2004)

Signaling to NF-{kappa}B
M. S. Hayden, and S. Ghosh
Genes Dev. 18, 2195-2224 (15 September 2004)

Detection of IKK{beta}-IKK{gamma} Subcomplexes in Monocytic Cells and Characterization of Associated Signaling
M. Quirling, S. Page, N. Jilg, K. Plenagl, D. Peus, C. Grubmuller, M. Weingartner, C. Fischer, D. Neumeier, K. Brand et al.
J Biol Chem 279, 37452-37460 (3 September 2004)

Toll-Like Receptor 9 Signaling Activates NF-{kappa}B through IFN Regulatory Factor-8/IFN Consensus Sequence Binding Protein in Dendritic Cells
H. Tsujimura, T. Tamura, H. J. Kong, A. Nishiyama, K. J. Ishii, D. M. Klinman, and K. Ozato
J. Immunol. 172, 6820-6827 (1 June 2004)

LRR-containing receptors regulating plant development and defense
A. Dievart, and S. E. Clark
Development 131, 251-261 (15 January 2004)

IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts
S. M. McWhirter, K. A. Fitzgerald, J. Rosains, D. C. Rowe, D. T. Golenbock, and T. Maniatis
Proc. Natl. Acad. Sci. USA 101, 233-238 (6 January 2004)

Biology of Toll receptors: lessons from insects and mammals
J.-L. Imler, and L. Zheng
J. Leukoc. Biol. 75, 18-26 (1 January 2004)

Computational Design of Variant TNF Molecules: A Novel Methodology for Inhibition of Proinflammatory Cascades
E. Abraham, and L. Zheng
Sci Signal 2003, pe51-pe51 (11 November 2003)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882