Skip to main content
SpringerLink
Log in

Innate Immune Signaling and Negative Regulators in Cancer

  • Chapter
  • First Online:
Innate Immune Regulation and Cancer Immunotherapy

Abstract

Innate immune pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors, and AIM2-like receptors (ALRs), function as pathogen pattern recognition molecules that sensor and initiate innate and adaptive immune responses against microbes and cancer cells. Recognition of pathogen-derived ligands by PRRs expressed on many types of cells, including dendritic cells (DCs) and T cells, triggers the NF-κB, type 1 interferon and inflammasome activation pathways, leading to the production of proinflammatory cytokines that are essential in inflammation and inflammation-linked cancer. Both positive and negative regulators are critical in the maintenance of innate immune homeostasis. In this review, I focus on the current understanding of PRRs, signaling pathways and their regulation through negative regulators. Their relevance to cancer will be discussed as well.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdul-Sater AA, Said-Sadier N, Lam VM, Singh B, Pettengill MA, Soares F, Tattoli I, Lipinski S, Girardin SE, Rosenstiel P et al (2010) Enhancement of reactive oxygen species production and chlamydial infection by the mitochondrial Nod-like family member NLRX1. J Biol Chem 285:41637–41645

    Article  PubMed  CAS  Google Scholar 

  • Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511

    Article  PubMed  CAS  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  PubMed  CAS  Google Scholar 

  • Alexander WS, Hilton DJ (2004) The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu Rev Immunol 22:503–529

    Article  PubMed  CAS  Google Scholar 

  • Alexander WS, Starr R, Fenner JE, Scott CL, Handman E, Sprigg NS, Corbin JE, Cornish AL, Darwiche R, Owczarek CM et al (1999) SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 98:597–608

    Article  PubMed  CAS  Google Scholar 

  • Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, Rogers AB, Herfarth HH, Jobin C, Ting JP (2010) The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 207:1045–1056

    Article  PubMed  CAS  Google Scholar 

  • Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K (2007) Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc Natl Acad Sci USA 104:7500–7505

    Article  PubMed  CAS  Google Scholar 

  • Arnoult D, Soares F, Tattoli I, Castanier C, Philpott DJ, Girardin SE (2009) An N-terminal addressing sequence targets NLRX1 to the mitochondrial matrix. J Cell Sci 122:3161–3168

    Article  PubMed  CAS  Google Scholar 

  • Asagiri M, Hirai T, Kunigami T, Kamano S, Gober HJ, Okamoto K, Nishikawa K, Latz E, Golenbock DT, Aoki K et al (2008) Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science 319:624–627

    Article  PubMed  CAS  Google Scholar 

  • Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C et al (2009) Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462:108–112

    Article  PubMed  CAS  Google Scholar 

  • Barton GM, Kagan JC, Medzhitov R (2006) Intracellular localization of Toll-like receptor 9 ­prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol 7:49–56

    Article  PubMed  CAS  Google Scholar 

  • Becker CE, O’Neill LA (2007) Inflammasomes in inflammatory disorders: the role of TLRs and their interactions with NLRs. Semin Immunopathol 29:239–248

    Article  PubMed  CAS  Google Scholar 

  • Benko S, Magalhaes JG, Philpott DJ, Girardin SE (2010) NLRC5 Limits the Activation of Inflammatory Pathways. J Immunol 185:1681–1691

    Article  PubMed  CAS  Google Scholar 

  • Bignell GR, Warren W, Seal S, Takahashi M, Rapley E, Barfoot R, Green H, Brown C, Biggs PJ, Lakhani SR et al (2000) Identification of the familial cylindromatosis tumour-suppressor gene. Nat Genet 25:160–165

    Article  PubMed  CAS  Google Scholar 

  • Bosanac I, Wertz IE, Pan B, Yu C, Kusam S, Lam C, Phu L, Phung Q, Maurer B, Arnott D et al (2010) Ubiquitin binding to A20 ZnF4 is required for modulation of NF-kappaB signaling. Mol Cell 40:548–557

    Article  PubMed  CAS  Google Scholar 

  • Brummelkamp TR, Nijman SM, Dirac AM, Bernards R (2003) Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature 424:797–801

    Article  PubMed  CAS  Google Scholar 

  • Burckstummer T, Baumann C, Bluml S, Dixit E, Durnberger G, Jahn H, Planyavsky M, Bilban M, Colinge J, Bennett KL (2009) An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol

    Google Scholar 

  • Chau TL, Gioia R, Gatot JS, Patrascu F, Carpentier I, Chapelle JP, O’Neill L, Beyaert R, Piette J, Chariot A (2008) Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated? Trends Biochem Sci 33:171–180

    Article  PubMed  CAS  Google Scholar 

  • Chen G, Shaw MH, Kim YG, Nunez G (2009) NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol 4:365–398

    Article  PubMed  CAS  Google Scholar 

  • Choe J, Kelker MS, Wilson IA (2005) Crystal structure of human toll-like receptor 3 (TLR3) ­ectodomain. Science 309:581–585

    Article  PubMed  CAS  Google Scholar 

  • Chuang TH, Ulevitch RJ (2004) Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat Immunol 5:495–502

    Article  PubMed  CAS  Google Scholar 

  • Clevers H (2004) At the crossroads of inflammation and cancer. Cell 118:671–674

    Article  PubMed  CAS  Google Scholar 

  • Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124:263–266

    Article  PubMed  CAS  Google Scholar 

  • Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P, Ferguson DJ, Campbell BJ, Jewell D, Simmons A (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16:90–97

    Article  PubMed  CAS  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed  CAS  Google Scholar 

  • Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ et al (2010) NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell 141:483–496

    Article  PubMed  CAS  Google Scholar 

  • Davis BK, Roberts RA, Huang MT, Willingham SB, Conti BJ, Brickey WJ, Barker BR, Kwan M, Taxman DJ, Accavitti-Loper MA et al (2011) Cutting Edge: NLRC5-Dependent Activation of the Inflammasome. J Immunol 186:1333–1337

    Article  PubMed  CAS  Google Scholar 

  • De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG (2007) Inflammation in prostate carcinogenesis. Nat Rev Cancer 7:256–269

    Article  PubMed  CAS  Google Scholar 

  • Deng JC, Cheng G, Newstead MW, Zeng X, Kobayashi K, Flavell RA, Standiford TJ (2006) Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. J Clin Invest 116:2532–2542

    PubMed  CAS  Google Scholar 

  • Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529–1531

    Article  PubMed  CAS  Google Scholar 

  • Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J (2008) Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320:674–677

    Article  PubMed  CAS  Google Scholar 

  • Duncan JA, Bergstralh DT, Wang Y, Willingham SB, Ye Z, Zimmermann AG, Ting JP (2007) Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. Proc Natl Acad Sci USA 104:8041–8046

    Article  PubMed  CAS  Google Scholar 

  • Dupaul-Chicoine J, Yeretssian G, Doiron K, Bergstrom KS, McIntire CR, LeBlanc PM, Meunier C, Turbide C, Gros P, Beauchemin N et al (2010) Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 32:367–378

    Article  PubMed  CAS  Google Scholar 

  • Eisenbarth SC, Colegio OR, O’Connor W, Sutterwala FS, Flavell RA (2008) Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453:1122–1126

    Article  PubMed  CAS  Google Scholar 

  • El-Omar EM, Ng MT, Hold GL (2008) Polymorphisms in Toll-like receptor genes and risk of cancer. Oncogene 27:244–252

    Article  PubMed  CAS  Google Scholar 

  • Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi GP, Chapman HA, Barton GM (2008) The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature 456:658–662

    Article  PubMed  CAS  Google Scholar 

  • Ewald SE, Engel A, Lee J, Wang M, Bogyo M, Barton GM (2011) Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J Exp Med

    Google Scholar 

  • Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES (2009) AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature

    Google Scholar 

  • Fernandes-Alnemri T, Yu JW, Juliana C, Solorzano L, Kang S, Wu J, Datta P, McCormick M, Huang L, McDermott E et al (2010) The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat Immunol 11:385–393

    Article  PubMed  CAS  Google Scholar 

  • Friedman CS, O’Donnell MA, Legarda-Addison D, Ng A, Cardenas WB, Yount JS, Moran TM, Basler CF, Komuro A, Horvath CM et al (2008) The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO Rep 9:930–936

    Article  PubMed  CAS  Google Scholar 

  • Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S et al (2007) TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446:916–920

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Navajas JM, Law J, Nguyen KP, Bhargava M, Corr MP, Varki N, Eckmann L, Hoffman HM, Lee J, Raz E (2010) Interleukin 1 receptor signaling regulates DUBA expression and facilitates Toll-like receptor 9-driven antiinflammatory cytokine production. J Exp Med 207:2799–2807

    Article  PubMed  CAS  Google Scholar 

  • Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–296

    Article  PubMed  CAS  Google Scholar 

  • Gulen MF, Kang Z, Bulek K, Youzhong W, Kim TW, Chen Y, Altuntas CZ, Sass Bak-Jensen K, McGeachy MJ, Do JS et al (2010) The receptor SIGIRR suppresses Th17 cell proliferation via inhibition of the interleukin-1 receptor pathway and mTOR kinase activation. Immunity 32:54–66

    Article  PubMed  CAS  Google Scholar 

  • Haverkamp J, Charbonneau B, Ratliff TL (2008) Prostate inflammation and its potential impact on prostate cancer: a current review. J Cell Biochem 103:1344–1353

    Article  PubMed  CAS  Google Scholar 

  • Hayakawa S, Shiratori S, Yamato H, Kameyama T, Kitatsuji C, Kashigi F, Goto S, Kameoka S, Fujikura D, Yamada T et al (2010) ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses. Nat Immunol 12:37–44

    Article  PubMed  CAS  Google Scholar 

  • Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303:1526–1529

    Article  PubMed  CAS  Google Scholar 

  • Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196–200

    Article  PubMed  CAS  Google Scholar 

  • Honda K, Taniguchi T (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6:644–658

    Article  PubMed  CAS  Google Scholar 

  • Honda K, Ohba Y, Yanai H, Negishi H, Mizutani T, Takaoka A, Taya C, Taniguchi T (2005a) Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434:1035–1040

    Article  PubMed  CAS  Google Scholar 

  • Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N et al (2005b) IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434:772–777

    Article  PubMed  CAS  Google Scholar 

  • Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann KK, Schlee M et al (2006) 5’-Triphosphate RNA is the ligand for RIG-I. Science 314:994–997

    Article  PubMed  Google Scholar 

  • Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey DR, Latz E, Fitzgerald KA (2009) AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature

    Google Scholar 

  • Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O’Morain CA, Gassull M et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603

    Article  PubMed  CAS  Google Scholar 

  • Inohara C, McDonald C, Nunez G (2005) NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu Rev Biochem 74:355–383

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa H, Barber GN (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455:674–678

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa H, Ma Z, Barber GN (2009) STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461:788–792

    Article  PubMed  CAS  Google Scholar 

  • Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995

    Article  PubMed  CAS  Google Scholar 

  • Janssens S, Beyaert R (2003) Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell 11:293–302

    Article  PubMed  CAS  Google Scholar 

  • Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, Lipford G, Bauer S (2002) Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol 3:499

    Article  PubMed  CAS  Google Scholar 

  • Kanneganti TD, Ozoren N, Body-Malapel M, Amer A, Park JH, Franchi L, Whitfield J, Barchet W, Colonna M, Vandenabeele P et al (2006) Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440:233–236

    Article  PubMed  CAS  Google Scholar 

  • Karin M, Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749–759

    Article  PubMed  CAS  Google Scholar 

  • Karin M, Lawrence T, Nizet V (2006) Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell 124:823–835

    Article  PubMed  CAS  Google Scholar 

  • Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujimura T, Takeda K, Fujita T, Takeuchi O et al (2005) Cell type-specific involvement of RIG-I in antiviral response. Immunity 23:19–28

    Article  PubMed  CAS  Google Scholar 

  • Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ et al (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105

    Article  PubMed  CAS  Google Scholar 

  • Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S (2008) Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 205:1601–1610

    Article  PubMed  CAS  Google Scholar 

  • Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J et al (2009) Frequent inactivation of A20 in B-cell lymphomas. Nature 459:712–716

    Article  PubMed  CAS  Google Scholar 

  • Kawagoe T, Takeuchi O, Takabatake Y, Kato H, Isaka Y, Tsujimura T, Akira S (2009) TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis. Nat Immunol 10:965–972

    Article  PubMed  CAS  Google Scholar 

  • Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S (2005) IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6:981–988

    Article  PubMed  CAS  Google Scholar 

  • Kayagaki N, Phung Q, Chan S, Chaudhari R, Quan C, O’Rourke KM, Eby M, Pietras E, Cheng G, Bazan JF et al (2007) DUBA: a deubiquitinase that regulates type I interferon production. Science 318:1628–1632

    Article  PubMed  CAS  Google Scholar 

  • Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S, Otageri P, Chandran B (2011) IFI16 Acts as a Nuclear Pathogen Sensor to Induce the Inflammasome in Response to Kaposi Sarcoma-Associated Herpesvirus Infection. Cell Host Microbe 9:363–375

    Article  PubMed  CAS  Google Scholar 

  • Kim YM, Brinkmann MM, Paquet ME, Ploegh HL (2008) UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature 452:234–238

    Article  PubMed  CAS  Google Scholar 

  • Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M, Yoshida H, Kubo M, Yoshimura A (2002) SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity 17:583–591

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi K, Hernandez LD, Galan JE, Janeway CA Jr, Medzhitov R, Flavell RA (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110:191–202

    Article  PubMed  CAS  Google Scholar 

  • Komander D, Lord CJ, Scheel H, Swift S, Hofmann K, Ashworth A, Barford D (2008) The structure of the CYLD USP domain explains its specificity for Lys63-linked polyubiquitin and reveals a B box module. Mol Cell 29:451–464

    Article  PubMed  CAS  Google Scholar 

  • Kovalenko A, Chable-Bessia C, Cantarella G, Israel A, Wallach D, Courtois G (2003) The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature 424:801–805

    Article  PubMed  CAS  Google Scholar 

  • Kuenzel S, Till A, Winkler M, Hasler R, Lipinski S, Jung S, Grotzinger J, Fickenscher H, Schreiber S, Rosenstiel P (2010) The nucleotide-binding oligomerization domain-like receptor NLRC5 is involved in IFN-dependent antiviral immune responses. J Immunol 184:1990–2000

    Article  PubMed  CAS  Google Scholar 

  • Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A (2000) Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 289:2350–2354

    Article  PubMed  CAS  Google Scholar 

  • Lee AJ, Zhou X, Chang M, Hunzeker J, Bonneau RH, Zhou D, Sun SC (2010) Regulation of natural killer T-cell development by deubiquitinase CYLD. EMBO J 29:1600–1612

    Article  PubMed  CAS  Google Scholar 

  • Lin WW, Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117:1175–1183

    Article  PubMed  CAS  Google Scholar 

  • Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill MA, Garcia-Sastre A, Katze MG et al (2008) Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 82:335–345

    Article  PubMed  CAS  Google Scholar 

  • Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 101:5598–5603

    Article  PubMed  CAS  Google Scholar 

  • Luo JL, Maeda S, Hsu LC, Yagita H, Karin M (2004) Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell 6:297–305

    Article  PubMed  CAS  Google Scholar 

  • Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, Kagnoff MF, Eckmann L, Karin M (2005a) Nod2 mutation in Crohn’s disease potentiates NF-kappaB activity and IL-1beta processing. Science 307:734–738

    Article  PubMed  CAS  Google Scholar 

  • Maeda S, Kamata H, Luo JL, Leffert H, Karin M (2005b) IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121:977–990

    Article  PubMed  CAS  Google Scholar 

  • Mariathasan S, Monack DM (2007) Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol 7:31–40

    Article  PubMed  CAS  Google Scholar 

  • Mariathasan S, Weiss DS, Newton K, McBride J, O’Rourke K, Roose-Girma M, Lee WP, Weinrauch Y, Monack DM, Dixit VM (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228–232

    Article  PubMed  CAS  Google Scholar 

  • Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN (1999) SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell 98:609–616

    Article  PubMed  CAS  Google Scholar 

  • Martinon F, Tschopp J (2005) NLRs join TLRs as innate sensors of pathogens. Trends Immunol 26:447–454

    Article  PubMed  CAS  Google Scholar 

  • Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241

    Article  PubMed  CAS  Google Scholar 

  • Massoumi R, Chmielarska K, Hennecke K, Pfeifer A, Fassler R (2006) Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling. Cell 125:665–677

    Article  PubMed  CAS  Google Scholar 

  • Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM, Sharp FA, Becker C, Franchi L, Yoshihara E, Chen Z et al (2010) Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol 11:897–904

    Article  PubMed  CAS  Google Scholar 

  • Meissner TB, Li A, Biswas A, Lee KH, Liu YJ, Bayir E, Iliopoulos D, van den Elsen PJ, Kobayashi KS (2010) NLR family member NLRC5 is a transcriptional regulator of MHC class I genes. Proc Natl Acad Sci USA

    Google Scholar 

  • Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437:1167–1172

    Article  PubMed  CAS  Google Scholar 

  • Meylan E, Dooley AL, Feldser DM, Shen L, Turk E, Ouyang C, Jacks T (2009) Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature 462:104–107

    Article  PubMed  CAS  Google Scholar 

  • Moore CB, Bergstralh DT, Duncan JA, Lei Y, Morrison TE, Zimmermann AG, Accavitti-Loper MA, Madden VJ, Sun L, Ye Z et al (2008) NLRX1 is a regulator of mitochondrial antiviral immunity. Nature 451:573–577

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa R, Naka T, Tsutsui H, Fujimoto M, Kimura A, Abe T, Seki E, Sato S, Takeuchi O, Takeda K et al (2002) SOCS-1 participates in negative regulation of LPS responses. Immunity 17:677–687

    Article  PubMed  CAS  Google Scholar 

  • Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP et al (2011) Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 12:222–230

    Article  PubMed  CAS  Google Scholar 

  • Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M (2007) Gender ­disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317:121–124

    Article  PubMed  CAS  Google Scholar 

  • Neerincx A, Lautz K, Menning M, Kremmer E, Zigrino P, Hosel M, Buning H, Schwarzenbacher R, Kufer TA (2010) A role for the human nucleotide-binding domain, leucine-rich repeat-containing family member NLRC5 in antiviral responses. J Biol Chem 285:26223–26232

    Article  PubMed  CAS  Google Scholar 

  • Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH et al (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    Article  PubMed  CAS  Google Scholar 

  • Opipari AW Jr, Boguski MS, Dixit VM (1990) The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. J Biol Chem 265:14705–14708

    PubMed  CAS  Google Scholar 

  • Oshiumi H, Miyashita M, Inoue N, Okabe M, Matsumoto M, Seya T (2010) The Ubiquitin Ligase Riplet Is Essential for RIG-I-Dependent Innate Immune Responses to RNA Virus Infection. Cell Host Microbe 8:496–509

    Article  PubMed  CAS  Google Scholar 

  • Park B, Brinkmann MM, Spooner E, Lee CC, Kim YM, Ploegh HL (2008) Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9. Nat Immunol 9:1407–1414

    Article  PubMed  CAS  Google Scholar 

  • Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, Wang DY, Li Y, Wang HY, Wang R-F (2005) Toll-like receptor 8 mediated-reversal of CD4+ regulatory T cell function. Science 309:1380–1384

    Article  PubMed  CAS  Google Scholar 

  • Peng G, Wang HY, Peng W, Kiniwa Y, Seo K, Wang R-F (2007) Tumor-infiltrating gamma-delta T cells suppress T and dendritic cell function via mechanisms controlled by a unique Toll-like receptor signaling pathway. Immunity 27:334–348

    Article  PubMed  CAS  Google Scholar 

  • Peto J (2001) Cancer epidemiology in the last century and the next decade. Nature 411:390–395

    Article  PubMed  CAS  Google Scholar 

  • Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, Reis e Sousa C (2006) RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates. Science 314:997–1001

    Article  PubMed  CAS  Google Scholar 

  • Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461–466

    Article  PubMed  CAS  Google Scholar 

  • Rakoff-Nahoum S, Medzhitov R (2007) Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science 317:124–127

    Article  PubMed  CAS  Google Scholar 

  • Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118:229–241

    Article  PubMed  CAS  Google Scholar 

  • Rathinam VA, Jiang Z, Waggoner SN, Sharma S, Cole LE, Waggoner L, Vanaja SK, Monks BG, Ganesan S, Latz E et al (2010) The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol 11:395–402

    Article  PubMed  CAS  Google Scholar 

  • Rehwinkel J, Tan CP, Goubau D, Schulz O, Pichlmair A, Bier K, Robb N, Vreede F, Barclay W, Fodor E et al (2010) RIG-I detects viral genomic RNA during negative-strand RNA virus ­infection. Cell 140:397–408

    Article  PubMed  CAS  Google Scholar 

  • Reiley WW, Zhang M, Jin W, Losiewicz M, Donohue KB, Norbury CC, Sun SC (2006) Regulation of T cell development by the deubiquitinating enzyme CYLD. Nat Immunol 7:411–417

    Article  PubMed  CAS  Google Scholar 

  • Reiley WW, Jin W, Lee AJ, Wright A, Wu X, Tewalt EF, Leonard TO, Norbury CC, Fitzpatrick L, Zhang M et al (2007) Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses. J Exp Med 204:1475–1485

    Article  PubMed  CAS  Google Scholar 

  • Roberts TL, Idris A, Dunn JA, Kelly GM, Burnton CM, Hodgson S, Hardy LL, Garceau V, Sweet MJ, Ross IL (2009) HIN-200 Proteins Regulate Caspase Activation in Response to Foreign Cytoplasmic DNA. Science

    Google Scholar 

  • Ryzhakov G, Randow F (2007) SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK. EMBO J 26:3180–3190

    Article  PubMed  CAS  Google Scholar 

  • Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S (2009) Activation of innate immune antiviral responses by Nod2. Nat Immunol 10:1073–1080

    Article  PubMed  CAS  Google Scholar 

  • Saha SK, Pietras EM, He JQ, Kang JR, Liu SY, Oganesyan G, Shahangian A, Zarnegar B, Shiba TL, Wang Y et al (2006) Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif. EMBO J 25:3257–3263

    Article  PubMed  CAS  Google Scholar 

  • Saito T, Hirai R, Loo YM, Owen D, Johnson CL, Sinha SC, Akira S, Fujita T, Gale M Jr (2007) Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA 104:582–587

    Article  PubMed  CAS  Google Scholar 

  • Saito T, Owen DM, Jiang F, Marcotrigiano J, Gale M Jr (2008) Innate immunity induced by ­composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature 454:523–527

    Article  PubMed  CAS  Google Scholar 

  • Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z, Dai RM, Wang E, Ma W, Haines D, O’HUigin C et al (2010) MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J Exp Med 207:1625–1636

    Article  PubMed  CAS  Google Scholar 

  • Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O (2010) LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proc Natl Acad Sci USA 107:1512–1517

    Article  PubMed  CAS  Google Scholar 

  • Schmitz R, Hansmann ML, Bohle V, Martin-Subero JI, Hartmann S, Mechtersheimer G, Klapper W, Vater I, Giefing M, Gesk S et al (2009) TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med 206:981–989

    Article  PubMed  CAS  Google Scholar 

  • Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832

    Article  PubMed  CAS  Google Scholar 

  • Seth RB, Sun L, Ea CK, Chen ZJ (2005) Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-kappaB and IRF3. Cell 122:669–682

    Article  PubMed  CAS  Google Scholar 

  • Shaw MH, Reimer T, Sanchez-Valdepenas C, Warner N, Kim YG, Fresno M, Nunez G (2009) T cell-intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii. Nat Immunol 10:1267–1274

    Article  PubMed  CAS  Google Scholar 

  • Shembade N, Harhaj NS, Parvatiyar K, Copeland NG, Jenkins NA, Matesic LE, Harhaj EW (2008) The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20. Nat Immunol 9:254–262

    Article  PubMed  CAS  Google Scholar 

  • Shembade N, Parvatiyar K, Harhaj NS, Harhaj EW (2009) The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling. EMBO J 28:513–522

    Article  PubMed  CAS  Google Scholar 

  • Shembade N, Ma A, Harhaj EW (2010) Inhibition of NF-kappaB signaling by A20 through ­disruption of ubiquitin enzyme complexes. Science 327:1135–1139

    Article  PubMed  CAS  Google Scholar 

  • Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA et al (1997) A family of cytokine-inducible inhibitors of signalling. Nature 387:917–921

    Article  PubMed  CAS  Google Scholar 

  • Sun SC (2008) Deubiquitylation and regulation of the immune response. Nat Rev Immunol 8:501–511

    Article  PubMed  CAS  Google Scholar 

  • Sun J, Wiklund F, Zheng SL, Chang B, Balter K, Li L, Johansson JE, Li G, Adami HO, Liu W et al (2005) Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. J Natl Cancer Inst 97:525–532

    Article  PubMed  CAS  Google Scholar 

  • Sutmuller RP, Morgan ME, Netea MG, Grauer O, Adema GJ (2006) Toll-like receptors on ­regulatory T cells: expanding immune regulation. Trends Immunol 27:387–393

    Article  PubMed  CAS  Google Scholar 

  • Sutterwala FS, Ogura Y, Szczepanik M, Lara-Tejero M, Lichtenberger GS, Grant EP, Bertin J, Coyle AJ, Galan JE, Askenase PW et al (2006) Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 24:317–327

    Article  PubMed  CAS  Google Scholar 

  • Suzuki N, Suzuki S, Duncan GS, Millar DG, Wada T, Mirtsos C, Takada H, Wakeham A, Itie A, Li S et al (2002) Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature 416:750–756

    Article  PubMed  CAS  Google Scholar 

  • Swann JB, Vesely MD, Silva A, Sharkey J, Akira S, Schreiber RD, Smyth MJ (2008) Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis. Proc Natl Acad Sci USA 105:652–656

    Article  PubMed  CAS  Google Scholar 

  • Tabeta K, Hoebe K, Janssen EM, Du X, Georgel P, Crozat K, Mudd S, Mann N, Sovath S, Goode J et al (2006) The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nat Immunol 7:156–164

    Article  PubMed  CAS  Google Scholar 

  • Takahasi K, Yoneyama M, Nishihori T, Hirai R, Kumeta H, Narita R, Gale M Jr, Inagaki F, Fujita T (2008) Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol Cell 29:428–440

    Article  PubMed  CAS  Google Scholar 

  • Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, Kano S, Honda K, Ohba Y, Mak TW et al (2005) Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434:243–249

    Article  PubMed  CAS  Google Scholar 

  • Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1–14

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi O, Akira S (2008) MDA5/RIG-I and virus recognition. Curr Opin Immunol 20:17–22

    Article  PubMed  CAS  Google Scholar 

  • Tattoli I, Carneiro LA, Jehanno M, Magalhaes JG, Shu Y, Philpott DJ, Arnoult D, Girardin SE (2008) NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-kappaB and JNK ­pathways by inducing reactive oxygen species production. EMBO Rep 9:293–300

    Article  PubMed  CAS  Google Scholar 

  • Thomassen E, Renshaw BR, Sims JE (1999) Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily. Cytokine 11:389–399

    Article  PubMed  CAS  Google Scholar 

  • Ting JP, Davis BK (2005) CATERPILLER: a novel gene family important in immunity, cell death, and diseases. Annu Rev Immunol 23:387–414

    Article  PubMed  CAS  Google Scholar 

  • Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG, Magalhaes JG, Yuan L, Soares F, Chea E, Le Bourhis L et al (2010) Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol 11:55–62

    Article  PubMed  CAS  Google Scholar 

  • Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G (2003) CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature 424:793–796

    Article  PubMed  CAS  Google Scholar 

  • Tsuchida T, Zou J, Saitoh T, Kumar H, Abe T, Matsuura Y, Kawai T, Akira S (2010) The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity 33:765–776

    Article  PubMed  CAS  Google Scholar 

  • Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, Sirois CM, Jin T, Latz E, Xiao TS et al (2010) IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol 11:997–1004

    Article  PubMed  CAS  Google Scholar 

  • Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, Towne J, Sims JE, Stark GR, Li X (2003) SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol 4:920–927

    Article  PubMed  CAS  Google Scholar 

  • Wertz IE, O’Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL et al (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430:694–699

    Article  PubMed  CAS  Google Scholar 

  • Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (1999) IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 274:19403–19410

    Article  PubMed  CAS  Google Scholar 

  • Xia X, Cui J, Wang HY, Zhu L, Matsueda S, Wang Q, Yang X, Hong J, Songyang Z, Chen Z et al (2011) NLRX1 negatively regulates TLR-induced NF-κB signaling by targeting TRAF6 and IKK. Immunity 34(6):843–853

    Article  PubMed  CAS  Google Scholar 

  • Xiao H, Gulen MF, Qin J, Yao J, Bulek K, Kish D, Altuntas CZ, Wald D, Ma C, Zhou H et al (2007) The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity 26:461–475

    Article  PubMed  CAS  Google Scholar 

  • Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB (2005) VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 19:727–740

    Article  PubMed  CAS  Google Scholar 

  • Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S et al (2005) TLR11 activation of dendritic cells by a ­protozoan profilin-like protein. Science 308:1626–1629

    Article  PubMed  CAS  Google Scholar 

  • Yoneyama M, Fujita T (2009) RNA recognition and signal transduction by RIG-I-like receptors. Immunol Rev 227:54–65

    Article  PubMed  CAS  Google Scholar 

  • Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (2004) The RNA helicase RIG-I has an essential function in double-stranded ­RNA-induced innate antiviral responses. Nat Immunol 5:730–737

    Article  PubMed  CAS  Google Scholar 

  • You F, Sun H, Zhou X, Sun W, Liang S, Zhai Z, Jiang Z (2009) PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4. Nat Immunol 10:1300–1308

    Article  PubMed  CAS  Google Scholar 

  • Yu Y, Hayward GS (2010) The ubiquitin E3 ligase RAUL negatively regulates type i interferon through ubiquitination of the transcription factors IRF7 and IRF3. Immunity 33:863–877

    Article  PubMed  CAS  Google Scholar 

  • Yu Y, Wang SE, Hayward GS (2005) The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22:59–70

    Article  PubMed  CAS  Google Scholar 

  • Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti TD (2010) The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32:379–391

    Article  PubMed  CAS  Google Scholar 

  • Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, Xu M, Chen ZJ (2010) Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 141:315–330

    Article  PubMed  CAS  Google Scholar 

  • Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, Ghosh S (2004) A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303:1522–1526

    Article  PubMed  CAS  Google Scholar 

  • Zheng SL, Augustsson-Balter K, Chang B, Hedelin M, Li L, Adami HO, Bensen J, Li G, Johnasson JE, Turner AR et al (2004) Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the CAncer Prostate in Sweden Study. Cancer Res 64:2918–2922

    Article  PubMed  CAS  Google Scholar 

  • Zhong B, Yang Y, Li S, Wang YY, Li Y, Diao F, Lei C, He X, Zhang L, Tien P et al (2008) The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 29:538–550

    Article  PubMed  CAS  Google Scholar 

  • Zhong B, Zhang L, Lei C, Li Y, Mao AP, Yang Y, Wang YY, Zhang XL, Shu HB (2009) The ­ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity 30:397–407

    Article  PubMed  CAS  Google Scholar 

  • Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–225

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work is in part supported by grants from National Institutes of Health and Cancer Research Institute.

Author information

Authors and Affiliations

  1. Departments of Pathology and Immunology, The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, 77030, USA

    Helen Y. Wang & Rong-Fu Wang

Authors
  1. Helen Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rong-Fu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rong-Fu Wang .

Editor information

Editors and Affiliations

  1. Center for Cell & Gene Therapy, Baylor College of Medicine, Baylor Plaza 1, Houston, 77030, Texas, USA

    Rongfu Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Wang, H.Y., Wang, RF. (2012). Innate Immune Signaling and Negative Regulators in Cancer. In: Wang, R. (eds) Innate Immune Regulation and Cancer Immunotherapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9914-6_6

Download citation

Publish with us

Policies and ethics

Search

Navigation