The roles of TLRs, RLRs and NLRs in pathogen recognition.

The mammalian innate immune system detects the presence of microbial infection through germ line-encoded pattern recognition receptors (PRRs). Toll-like receptors, retinoic acid-inducible gene-I-like receptors and nucleotide-binding oligomerization domain-like receptors serve as PRRs that recognize different but overlapping microbial components. They are expressed in different cellular compartments such as the cell surface, endosome, lysosome or cytoplasm and activate specific signaling pathways that lead to expression of genes that tailor immune responses to particular microbes. This review summarizes recent insights into pathogen sensing by these PRRs and their signaling pathways.

[1]  G. Barber,et al.  STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling , 2008, Nature.

[2]  S. Akira,et al.  Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production , 2008, Nature.

[3]  Sarah L. Brown,et al.  A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells , 2008, Nature.

[4]  H. Ploegh,et al.  Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9 , 2008, Nature Immunology.

[5]  Y. Li,et al.  The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. , 2008, Immunity.

[6]  Masahiro Yamamoto,et al.  ATP drives lamina propria TH17 cell differentiation , 2008, Nature.

[7]  Sky W. Brubaker,et al.  Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin , 2008, Nature Immunology.

[8]  O. Ramilo,et al.  MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus , 2008, Proceedings of the National Academy of Sciences.

[9]  Sarah E. Ewald,et al.  The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor , 2008, Nature.

[10]  B. Finlay,et al.  The caspase-1 inflammasome: a pilot of innate immune responses. , 2008, Cell host & microbe.

[11]  Zheng‐gang Liu,et al.  The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors , 2008, Nature Immunology.

[12]  George Kollias,et al.  Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses , 2008, Nature Immunology.

[13]  J. Arthur,et al.  The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling , 2008, Nature Immunology.

[14]  T. Heidmann,et al.  Trex1 Prevents Cell-Intrinsic Initiation of Autoimmunity , 2008, Cell.

[15]  M. Yoneyama,et al.  Structural mechanism of RNA recognition by the RIG-I-like receptors. , 2008, Immunity.

[16]  Jie-Oh Lee,et al.  Structures of the toll-like receptor family and its ligand complexes. , 2008, Immunity.

[17]  A. Bowie,et al.  Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKε‐mediated IRF activation , 2008, The EMBO journal.

[18]  R. Higgs,et al.  The E3 Ubiquitin Ligase Ro52 Negatively Regulates IFN-β Production Post-Pathogen Recognition by Polyubiquitin-Mediated Degradation of IRF31 , 2008, The Journal of Immunology.

[19]  Yun-Gi Kim,et al.  NOD-like receptors (NLRs): bona fide intracellular microbial sensors. , 2008, Current opinion in immunology.

[20]  G. Núñez,et al.  The Nlrp3 inflammasome is critical for aluminium hydroxide‐mediated IL‐1β secretion but dispensable for adjuvant activity , 2008, European journal of immunology.

[21]  M. Gilliet,et al.  Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases , 2008, Nature Reviews Immunology.

[22]  K. Rock,et al.  Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization , 2008, Nature Immunology.

[23]  L. O’Neill.  When signaling pathways collide: positive and negative regulation of toll-like receptor signal transduction. , 2008, Immunity.

[24]  K. Moore,et al.  The NALP3 inflammasome is involved in the innate immune response to amyloid-β , 2008, Nature Immunology.

[25]  S. Akira,et al.  Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation–associated gene 5 , 2008, The Journal of experimental medicine.

[26]  F. Re,et al.  Cutting Edge: Inflammasome Activation by Alum and Alum’s Adjuvant Effect Are Mediated by NLRP31 , 2008, The Journal of Immunology.

[27]  Michael Gale,et al.  Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA , 2008, Nature.

[28]  Hiroshi Kiyono,et al.  Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5 , 2008, Nature Immunology.

[29]  Richard A. Flavell,et al.  The Nalp3 inflammasome is essential for the development of silicosis , 2008, Proceedings of the National Academy of Sciences.

[30]  A. Bauch,et al.  The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response , 2008, The EMBO journal.

[31]  Richard A. Flavell,et al.  Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants , 2008, Nature.

[32]  A. Rubartelli,et al.  ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1β and IL-18 secretion in an autocrine way , 2008, Proceedings of the National Academy of Sciences.

[33]  V. Nizet,et al.  A NOD2–NALP1 complex mediates caspase-1-dependent IL-1β secretion in response to Bacillus anthracis infection and muramyl dipeptide , 2008, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Osamu Takeuchi,et al.  Sequential control of Toll-like receptor–dependent responses by IRAK1 and IRAK2 , 2008, Nature Immunology.

[35]  J. Tschopp,et al.  TRADD protein is an essential component of the RIG-like helicase antiviral pathway. , 2008, Immunity.

[36]  J. Tschopp,et al.  Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica , 2008, Science.

[37]  Xuetao Cao,et al.  Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1 , 2008, Nature Immunology.

[38]  Justine R. Smith,et al.  Sequence- and target-independent angiogenesis suppression by siRNA via TLR3 , 2008, Nature.

[39]  K. Miyake,et al.  Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. , 2008, Biochemical and biophysical research communications.

[40]  K. Miyake,et al.  Cathepsins are required for Toll-like receptor 9 responses. , 2008, Biochemical and biophysical research communications.

[41]  Lois J. Maltais,et al.  The NLR gene family: a standard nomenclature. , 2008, Immunity.

[42]  E. Latz,et al.  The DNA sugar backbone 2' deoxyribose determines toll-like receptor 9 activation. , 2008, Immunity.

[43]  D. Philpott,et al.  The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals. , 2008, Immunity.

[44]  H. Ploegh,et al.  UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes , 2008, Nature.

[45]  J. Tschopp,et al.  The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response , 2008, Nature.

[46]  D. Philpott,et al.  NLRX1 is a mitochondrial NOD‐like receptor that amplifies NF‐κB and JNK pathways by inducing reactive oxygen species production , 2008, EMBO reports.

[47]  F. Inagaki,et al.  Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. , 2008, Molecular cell.

[48]  S. Akira,et al.  TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β , 2008, Nature Immunology.

[49]  C. Coban,et al.  Malaria Parasites Require TLR9 Signaling for Immune Evasion by Activating Regulatory T Cells1 , 2008, The Journal of Immunology.

[50]  Marie-France Carlier,et al.  Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response. , 2008, Cell host & microbe.

[51]  R. Coffman,et al.  PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation , 2008, The Journal of experimental medicine.

[52]  C. Coban,et al.  TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines , 2008, Nature.

[53]  J. Casanova,et al.  Novel primary immunodeficiencies revealed by the investigation of paediatric infectious diseases. , 2008, Current opinion in immunology.

[54]  K. Conzelmann,et al.  The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I. , 2008, Molecular cell.

[55]  K. Miyazono,et al.  Cathepsin K-Dependent Toll-Like Receptor 9 Signaling Revealed in Experimental Arthritis , 2008, Science.

[56]  M. Boutros,et al.  Akirins are highly conserved nuclear proteins required for NF-κB-dependent gene expression in drosophila and mice , 2008, Nature Immunology.

[57]  M. Heise,et al.  NLRX1 is a regulator of mitochondrial antiviral immunity , 2008, Nature.

[58]  P. Lucas,et al.  A critical role of RICK/RIP2 polyubiquitination in Nod‐induced NF‐κB activation , 2008 .

[59]  K. Ishii,et al.  Cutting Edge: Cooperation of IPS-1- and TRIF-Dependent Pathways in Poly IC-Enhanced Antibody Production and Cytotoxic T Cell Responses , 2008, The Journal of Immunology.

[60]  M. Boutros,et al.  Akirins, highly conserved nuclear proteins, required for NF-κB dependent gene expression in Drosophila and mice , 2007, Nature Immunology.

[61]  J. Banchereau,et al.  Pyogenic Bacterial Infections in Humans with MyD88 Deficiency , 2003, Science.

[62]  H. Hammad,et al.  Cutting Edge Cutting Edge : Alum Adjuvant Stimulates Inflammatory Dendritic Cells through Activation of the NALP 3 Inflammasome , 2008 .

[63]  P. Lucas,et al.  A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. , 2008, The EMBO journal.

[64]  D. Green,et al.  Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis , 2007, Nature.

[65]  G. Lemke,et al.  TAM Receptors Are Pleiotropic Inhibitors of the Innate Immune Response , 2007, Cell.

[66]  E. Pietras,et al.  A Deubiquitinase That Regulates Type I Interferon Production , 2007, Science.

[67]  J. Ward,et al.  Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. , 2007, Immunity.

[68]  D. Hommes,et al.  Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. , 2007, Immunity.

[69]  Gabriel Núñez,et al.  Intracellular NOD-like receptors in host defense and disease. , 2007, Immunity.

[70]  S. Akira,et al.  Lymphocytoid Choriomeningitis Virus Activates Plasmacytoid Dendritic Cells and Induces a Cytotoxic T-Cell Response via MyD88 , 2007, Journal of Virology.

[71]  R. Medzhitov.  Recognition of microorganisms and activation of the immune response , 2007, Nature.

[72]  I. Mellman,et al.  Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide , 2007, Nature.

[73]  Shohei Koyama,et al.  Differential Role of TLR- and RLR-Signaling in the Immune Responses to Influenza A Virus Infection and Vaccination , 2007, The Journal of Immunology.

[74]  Osamu Takeuchi,et al.  Genetic analysis of resistance to viral infection , 2007, Nature Reviews Immunology.

[75]  S. Paik,et al.  Crystal Structure of the TLR1-TLR2 Heterodimer Induced by Binding of a Tri-Acylated Lipopeptide , 2007, Cell.

[76]  A. Smahi,et al.  TLR3 Deficiency in Patients with Herpes Simplex Encephalitis , 2007, Science.

[77]  Hayyoung Lee,et al.  Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran , 2007, Cell.

[78]  J. Tschopp,et al.  From inflammasomes to fevers, crystals and hypertension: how basic research explains inflammatory diseases. , 2007, Trends in molecular medicine.

[79]  F. Martinon,et al.  Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration , 2007, Cell Death and Differentiation.

[80]  J. Lieberman,et al.  Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus , 2007, Nature Genetics.

[81]  A. Miyawaki,et al.  The Atg5–Atg12 conjugate associates with innate antiviral immune responses , 2007, Proceedings of the National Academy of Sciences.

[82]  S. Akira,et al.  Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses. , 2007, Immunity.

[83]  Lucia Gabriele,et al.  The feedback phase of type I interferon induction in dendritic cells requires interferon regulatory factor 8. , 2007, Immunity.

[84]  R. Silverman,et al.  Small self-RNA generated by RNase L amplifies antiviral innate immunity , 2007, Nature.

[85]  K. Honda,et al.  DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response , 2007, Nature.

[86]  Z. Zhai,et al.  Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase , 2007, Proceedings of the National Academy of Sciences.

[87]  S. Werner,et al.  The Inflammasome Mediates UVB-Induced Activation and Secretion of Interleukin-1β by Keratinocytes , 2007, Current Biology.

[88]  Hyun Kook Cho,et al.  Cutting Edge: Autoantigen Ro52 Is an Interferon Inducible E3 Ligase That Ubiquitinates IRF-8 and Enhances Cytokine Expression in Macrophages1 , 2007, The Journal of Immunology.

[89]  D. Lin,et al.  Fen1 mutations result in autoimmunity, chronic inflammation and cancers , 2007, Nature Medicine.

[90]  G. Dubyak,et al.  Differential Requirement of P2X7 Receptor and Intracellular K+ for Caspase-1 Activation Induced by Intracellular and Extracellular Bacteria* , 2007, Journal of Biological Chemistry.

[91]  Y. Satow,et al.  Crystal Structures of Human MD-2 and Its Complex with Antiendotoxic Lipid IVa , 2007, Science.

[92]  原田 寿郎,et al.  Interleukin-1 Receptor-Associated Kinase 4 , 2007 .

[93]  J. Ruland,et al.  Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17 , 2007, Nature Immunology.

[94]  J. Penninger,et al.  The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors , 2007, Nature Immunology.

[95]  G. Barber,et al.  Loss of DExD/H Box RNA Helicase LGP2 Manifests Disparate Antiviral Responses , 2007, The Journal of Immunology.

[96]  B. Beutler,et al.  TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity , 2007, Nature Medicine.

[97]  F. Martinon,et al.  A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses , 2007, Nature Immunology.

[98]  Hideyuki Konishi,et al.  Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125 , 2007, Proceedings of the National Academy of Sciences.

[99]  T. Kaisho,et al.  PDLIM2-mediated termination of transcription factor NF-κB activation by intranuclear sequestration and degradation of the p65 subunit , 2007, Nature Immunology.

[100]  D. Philpott,et al.  Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity. , 2007, Immunity.

[101]  P. Vandenabeele,et al.  Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. , 2007, Immunity.

[102]  H. Ploegh,et al.  The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling , 2007, The Journal of cell biology.

[103]  Osamu Takeuchi,et al.  TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity , 2007, Nature.

[104]  R. Ulevitch,et al.  SGT1 is essential for Nod1 activation , 2007, Proceedings of the National Academy of Sciences.

[105]  L. Audoly,et al.  Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE , 2007, Nature Immunology.

[106]  A. Osterman,et al.  Bcl-2 and Bcl-XL Regulate Proinflammatory Caspase-1 Activation by Interaction with NALP1 , 2007, Cell.

[107]  A. Iwasaki,et al.  Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells , 2007, Science.

[108]  G. Núñez,et al.  RICK/RIP2 Mediates Innate Immune Responses Induced through Nod1 and Nod2 but Not TLRs1 , 2007, The Journal of Immunology.

[109]  B. Monks,et al.  Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9 , 2007, Proceedings of the National Academy of Sciences.

[110]  F. Schmitz,et al.  Interferon‐regulatory‐factor 1 controls Toll‐like receptor 9‐mediated IFN‐β production in myeloid dendritic cells , 2007 .

[111]  K. Miyake.  Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. , 2007, Seminars in immunology.

[112]  X. Qin,et al.  The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens , 2007, Nature Immunology.

[113]  A. Surprenant,et al.  Pannexin-1 Couples to Maitotoxin- and Nigericin-induced Interleukin-1β Release through a Dye Uptake-independent Pathway* , 2007, Journal of Biological Chemistry.

[114]  J. Miyoshi,et al.  Antitumor NK activation induced by the Toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells , 2007, Proceedings of the National Academy of Sciences.

[115]  S. Gordon,et al.  Dectin-1 is required for beta-glucan recognition and control of fungal infection. , 2007, Nature immunology.

[116]  F. Schmitz,et al.  Interferon-regulatory-factor 1 controls Toll-like receptor 9-mediated IFN-beta production in myeloid dendritic cells. , 2007, European journal of immunology.

[117]  S. Akira,et al.  Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans , 2007, Nature Immunology.

[118]  Thomas Lengauer,et al.  A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 , 2007, Nature Genetics.

[119]  David Miller,et al.  Critical Role for Cryopyrin/Nalp3 in Activation of Caspase-1 in Response to Viral Infection and Double-stranded RNA*> , 2006, Journal of Biological Chemistry.

[120]  C. Qian,et al.  SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production. , 2006, Immunity.

[121]  D. Philpott,et al.  Nod-like proteins in immunity, inflammation and disease , 2006, Nature Immunology.

[122]  Graham F. Brady,et al.  Regulation of Legionella Phagosome Maturation and Infection through Flagellin and Host Ipaf* , 2006, Journal of Biological Chemistry.

[123]  Jonathan D. G. Jones,et al.  The plant immune system , 2006, Nature.

[124]  Gunther Hartmann,et al.  5'-Triphosphate RNA Is the Ligand for RIG-I , 2006, Science.

[125]  A. Pichlmair,et al.  RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5'-Phosphates , 2006, Science.

[126]  K. Ishii,et al.  Innate immune recognition of, and regulation by, DNA. , 2006, Trends in immunology.

[127]  A. Surprenant,et al.  Pannexin‐1 mediates large pore formation and interleukin‐1β release by the ATP‐gated P2X7 receptor , 2006, The EMBO journal.

[128]  H. Yoshikawa,et al.  Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages , 2006, Nature.

[129]  Hiroshi Takayanagi,et al.  Evidence for licensing of IFN-γ-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program , 2006, Proceedings of the National Academy of Sciences.

[130]  J. Tschopp,et al.  Caspase-1 Activation of Lipid Metabolic Pathways in Response to Bacterial Pore-Forming Toxins Promotes Cell Survival , 2006, Cell.

[131]  R. Medzhitov,et al.  Type I interferons in host defense. , 2006, Immunity.

[132]  J. Ruland,et al.  Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity , 2006, Nature.

[133]  E. Pietras,et al.  Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif , 2006, The EMBO journal.

[134]  K. Ishii,et al.  Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling , 2006, Nature Immunology.

[135]  F. Chen,et al.  Finding NEMO by K63-linked polyubiquitin chain , 2006, Cell Death and Differentiation.

[136]  D. Barnes,et al.  Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus , 2006, Nature Genetics.

[137]  C. Coban,et al.  Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells , 2006, Nature Immunology.

[138]  Michael Karin,et al.  Intracellular pattern recognition receptors in the host response , 2006, Nature.

[139]  A. Satterthwaite,et al.  Autoreactive B Cell Responses to RNA-Related Antigens Due to TLR7 Gene Duplication , 2006, Science.

[140]  N. Gay,et al.  Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[141]  R. Medzhitov,et al.  Phosphoinositide-Mediated Adaptor Recruitment Controls Toll-like Receptor Signaling , 2006, Cell.

[142]  S. Akira,et al.  Innate immune recognition of viral infection. , 2006, Nature immunology.

[143]  J. Bertin,et al.  Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages , 2006, Nature Immunology.

[144]  Alan Aderem,et al.  Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf , 2006, Nature Immunology.

[145]  Lena Alexopoulou,et al.  Detrimental Contribution of the Toll-Like Receptor (TLR)3 to Influenza A Virus–Induced Acute Pneumonia , 2006, PLoS pathogens.

[146]  D. Clayton,et al.  A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region , 2006, Nature Genetics.

[147]  K. Ishii,et al.  Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses , 2006, Nature.

[148]  Paul A. Serbinowski,et al.  A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells , 2006, Nature Biotechnology.

[149]  M. Swanson,et al.  Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection , 2006, The Journal of experimental medicine.

[150]  Marta E Alarcón-Riquelme,et al.  A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus , 2006, Nature Genetics.

[151]  S. Akira,et al.  Cutting Edge: Roles of Caspase-8 and Caspase-10 in Innate Immune Responses to Double-Stranded RNA , 2006, The Journal of Immunology.

[152]  L. Glimcher,et al.  Osteopontin expression is essential for interferon-α production by plasmacytoid dendritic cells , 2006, Nature Immunology.

[153]  S. Akira,et al.  IκB kinase-α is critical for interferon-α production induced by Toll-like receptors 7 and 9 , 2006, Nature.

[154]  V. Dixit,et al.  Cryopyrin activates the inflammasome in response to toxins and ATP , 2006, Nature.

[155]  S. Akira,et al.  Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3 , 2006, Nature.

[156]  F. Martinon,et al.  Gout-associated uric acid crystals activate the NALP3 inflammasome , 2006, Nature.

[157]  J. Bertin,et al.  Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. , 2006, Immunity.

[158]  D. Kastner,et al.  CATERPILLERs, pyrin and hereditary immunological disorders , 2006, Nature Reviews Immunology.

[159]  W. Dietrich,et al.  Flagellin-Deficient Legionella Mutants Evade Caspase-1- and Naip5-Mediated Macrophage Immunity , 2006, PLoS pathogens.

[160]  S. Akira,et al.  Pathogen Recognition and Innate Immunity , 2006, Cell.

[161]  W. Dietrich,et al.  The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection , 2006, Nature Immunology.

[162]  W. Dietrich,et al.  Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin , 2006, Nature Genetics.

[163]  S. Grinstein,et al.  The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9 , 2006, Nature Immunology.

[164]  M. Mann,et al.  Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6 , 2006, Nature.

[165]  A. Shahangian,et al.  Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response , 2006, Nature.

[166]  S. Akira,et al.  IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9. , 2006, Nature.

[167]  R. Medzhitov,et al.  Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. , 2006, Immunity.

[168]  S. Akira,et al.  TLR signaling. , 2006, Current topics in microbiology and immunology.

[169]  L. Glimcher,et al.  Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. , 2006, Nature immunology.

[170]  R. Medzhitov,et al.  Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA , 2006, Nature Immunology.

[171]  C. Coban,et al.  A Toll-like receptor–independent antiviral response induced by double-stranded B-form DNA , 2006, Nature Immunology.

[172]  S. Akira,et al.  Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8 , 2005, The Journal of experimental medicine.

[173]  H. S. Warren,et al.  Toll-like receptors. , 2005, Critical care medicine.

[174]  S. Akira,et al.  Toll-like receptor–independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation , 2005, The Journal of experimental medicine.

[175]  Ki-Young Lee,et al.  TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. , 2005, Genes & development.

[176]  S. Akira,et al.  RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement , 2005, The Journal of experimental medicine.

[177]  A. DeFranco,et al.  TLR3 and TLR7 Are Targeted to the Same Intracellular Compartments by Distinct Regulatory Elements*♦ , 2005, Journal of Biological Chemistry.

[178]  Ralf Bartenschlager,et al.  Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus , 2005, Nature.

[179]  K. Takeda.  [Toll-like receptor]. , 2005, Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology.

[180]  Osamu Takeuchi,et al.  IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction , 2005, Nature Immunology.

[181]  D. Underhill,et al.  Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. , 2005, Blood.

[182]  S. Akira,et al.  Essential function for the kinase TAK1 in innate and adaptive immune responses , 2005, Nature Immunology.

[183]  Z. Zhai,et al.  VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling , 2005 .

[184]  Zhijian J. Chen,et al.  Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3 , 2005, Cell.

[185]  I. Wilson,et al.  Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain , 2005, Science.

[186]  Osamu Takeuchi,et al.  Cell type-specific involvement of RIG-I in antiviral response. , 2005, Immunity.

[187]  M. Chamaillard,et al.  NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. , 2005, Annual review of biochemistry.

[188]  J. Andersen,et al.  TLR11 Activation of Dendritic Cells by a Protozoan Profilin-Like Protein , 2005, Science.

[189]  Zhengfan Jiang,et al.  CD14 is required for MyD88-independent LPS signaling , 2005, Nature Immunology.

[190]  K. Honda,et al.  Spatiotemporal regulation of MyD88–IRF-7 signalling for robust type-I interferon induction , 2005, Nature.

[191]  Hideo Negishi,et al.  IRF-7 is the master regulator of type-I interferon-dependent immune responses , 2005, Nature.

[192]  S. Gordon,et al.  Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. , 2005, Immunity.

[193]  C. Coban,et al.  Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction , 2005, The Journal of experimental medicine.

[194]  Tak W. Mak,et al.  Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors , 2005, Nature.

[195]  R. Flavell,et al.  Toll-like receptor 3 promotes cross-priming to virus-infected cells , 2005, Nature.

[196]  Richard A. Flavell,et al.  Nod2-Dependent Regulation of Innate and Adaptive Immunity in the Intestinal Tract , 2005, Science.

[197]  Thomas Hartung,et al.  CD36 is a sensor of diacylglycerides , 2005, Nature.

[198]  D. Golenbock,et al.  Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. , 2005, The Journal of clinical investigation.

[199]  C. Coban,et al.  Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin , 2005, The Journal of experimental medicine.

[200]  Zhijian J. Chen,et al.  Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. , 2005, Cell.

[201]  M. Colonna,et al.  Plasmacytoid dendritic cells , 2005, Immunologic research.

[202]  Z. Zhai,et al.  VISA is an adapter protein required for virus-triggered IFN-beta signaling. , 2005, Molecular cell.

[203]  H. Yoshida,et al.  Lethal anemia caused by interferon-β produced in mouse embryos carrying undigested DNA , 2005, Nature Immunology.

[204]  E. Fikrig,et al.  Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis , 2004, Nature Medicine.

[205]  G. Barber,et al.  A FADD-dependent innate immune mechanism in mammalian cells , 2004, Nature.

[206]  F. Martinon,et al.  Identification of Bacterial Muramyl Dipeptide as Activator of the NALP3/Cryopyrin Inflammasome , 2004, Current Biology.

[207]  John Bertin,et al.  Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island , 2004, Nature Immunology.

[208]  K. Honda,et al.  Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[209]  A. Schaeffer.  A Toll-Like Receptor That Prevents Infection by Uropathogenic Bacteria , 2004 .

[210]  C. Coban,et al.  Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6 , 2004, Nature Immunology.

[211]  J. Cedarbaum.  Survival , 2004 .

[212]  S. Akira,et al.  Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ , 2004, Nature.

[213]  S. Akira,et al.  TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. , 2004, Immunity.

[214]  K. Ishii,et al.  Toll-Like Receptor 9 Signaling Activates NF-κB through IFN Regulatory Factor-8/IFN Consensus Sequence Binding Protein in Dendritic Cells1 , 2004, The Journal of Immunology.

[215]  K. Tyler,et al.  Does Toll-like receptor 3 play a biological role in virus infections? , 2004, Virology.

[216]  V. A. Stewart,et al.  Malaria Blood Stage Parasites Activate Human Plasmacytoid Dendritic Cells and Murine Dendritic Cells through a Toll-Like Receptor 9-Dependent Pathway1 , 2004, The Journal of Immunology.

[217]  Akiko Iwasaki,et al.  Recognition of single-stranded RNA viruses by Toll-like receptor 7. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[218]  R. Flavell,et al.  Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[219]  Shizuo Akira,et al.  Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA , 2004, Science.

[220]  S. Akira,et al.  Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8 , 2004, Science.

[221]  S. Akira,et al.  Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. , 2004, Blood.

[222]  B. Monks,et al.  TLR9 signals after translocating from the ER to CpG DNA in the lysosome , 2004, Nature Immunology.

[223]  S. Akira,et al.  Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta. , 2004, Nature.

[224]  J. Hoffmann,et al.  The immune response of Drosophila , 2003, Nature.

[225]  S. Akira,et al.  Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells , 2003, The Journal of experimental medicine.

[226]  S. Foster,et al.  An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid , 2003, Nature Immunology.

[227]  J. Bertin,et al.  Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan , 2003, Science.

[228]  Guo-Ping Zhou,et al.  Triggering the Interferon Antiviral Response Through an IKK-Related Pathway , 2003, Science.

[229]  Shizuo Akira,et al.  Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2 , 2003, The Journal of experimental medicine.

[230]  邊見 弘明,et al.  A Toll-like receptor recognizes bacterial DNA , 2003 .

[231]  M. Chamaillard,et al.  Nod2 Is a General Sensor of Peptidoglycan through Muramyl Dipeptide (MDP) Detection* , 2003, The Journal of Biological Chemistry.

[232]  S. Foster,et al.  Host Recognition of Bacterial Muramyl Dipeptide Mediated through NOD2 , 2003, The Journal of Biological Chemistry.

[233]  T. Maniatis,et al.  IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. , 2003, Nature immunology.

[234]  M. Shlomchik,et al.  Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors , 2002, Nature.

[235]  S. Akira,et al.  Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway , 2002, Nature Immunology.

[236]  C. Janeway,et al.  Innate immune recognition. , 2002, Annual review of immunology.

[237]  R. Flavell,et al.  Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 , 2001, Nature.

[238]  T. Horiuchi,et al.  Mutation of DNASE1 in people with systemic lupus erythematosus , 2001, Nature Genetics.

[239]  S. Akira,et al.  The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 , 2001, Nature.

[240]  T. Möröy,et al.  Features of systemic lupus erythematosus in Dnase1-deficient mice , 2000, Nature Genetics.

[241]  S. Akira,et al.  Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. , 1999, Journal of immunology.

[242]  P. Ricciardi-Castagnoli,et al.  Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. , 1998, Science.

[243]  C. Janeway,et al.  A human homologue of the Drosophila Toll protein signals activation of adaptive immunity , 1997, Nature.

[244]  C. Janeway.  Approaching the asymptote? Evolution and revolution in immunology. , 1989, Cold Spring Harbor symposia on quantitative biology.

[245]  W. Wooster,et al.  Crystal structure of , 2005 .