The Inflammasome in Host Defense

Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes.

[1]  J. Tschopp,et al.  Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors , 2009, Nature Medicine.

[2]  D. Soll,et al.  Cutting Edge: Candida albicans Hyphae Formation Triggers Activation of the Nlrp3 Inflammasome1 , 2009, The Journal of Immunology.

[3]  N. Bostanci,et al.  Expression and regulation of the NALP3 inflammasome complex in periodontal diseases , 2009, Clinical and experimental immunology.

[4]  J. Tschopp,et al.  Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal , 2009, PloS one.

[5]  J. Mogridge,et al.  Expression of Nlrp1b Inflammasome Components in Human Fibroblasts Confers Susceptibility to Anthrax Lethal Toxin , 2009, Infection and Immunity.

[6]  I. Brodsky,et al.  NLR-mediated control of inflammasome assembly in the host response against bacterial pathogens. , 2009, Seminars in immunology.

[7]  J. Hiscott,et al.  RIG-I-like receptors: sensing and responding to RNA virus infection. , 2009, Seminars in immunology.

[8]  F. Sutterwala,et al.  Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases , 2009, PLoS pathogens.

[9]  D. Ojcius,et al.  Inflammasome-dependent Caspase-1 Activation in Cervical Epithelial Cells Stimulates Growth of the Intracellular Pathogen Chlamydia trachomatis* , 2009, The Journal of Biological Chemistry.

[10]  S. Leppla,et al.  CA-074Me Protection against Anthrax Lethal Toxin , 2009, Infection and Immunity.

[11]  J. Tschopp,et al.  T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes , 2009, Nature.

[12]  R. Medzhitov Approaching the asymptote: 20 years later. , 2009, Immunity.

[13]  M. Lamkanfi,et al.  Fungal Zymosan and Mannan Activate the Cryopyrin Inflammasome* , 2009, The Journal of Biological Chemistry.

[14]  K. Fitzgerald,et al.  An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. , 2009, Cell host & microbe.

[15]  J. Tschopp,et al.  Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence , 2009, Nature.

[16]  H. Wolff,et al.  Trichothecene Mycotoxins Activate Inflammatory Response in Human Macrophages1 , 2009, The Journal of Immunology.

[17]  M. Huang,et al.  Neisseria gonorrhoeae Activates the Proteinase Cathepsin B to Mediate the Signaling Activities of the NLRP3 and ASC-Containing Inflammasome1 , 2009, The Journal of Immunology.

[18]  M. Murakami,et al.  Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria , 2009, The Journal of experimental medicine.

[19]  J. P. de Rivero Vaccari,et al.  The Pannexin 1 Channel Activates the Inflammasome in Neurons and Astrocytes* , 2009, The Journal of Biological Chemistry.

[20]  K. Shirasu The HSP90-SGT1 chaperone complex for NLR immune sensors. , 2009, Annual review of plant biology.

[21]  R. Webby,et al.  The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. , 2009, Immunity.

[22]  J. Ting,et al.  The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. , 2009, Immunity.

[23]  L. Joosten,et al.  Bypassing pathogen-induced inflammasome activation for the regulation of interleukin-1beta production by the fungal pathogen Candida albicans. , 2009, The Journal of infectious diseases.

[24]  C. Marsh,et al.  Caspase-7 Activation by the Nlrc4/Ipaf Inflammasome Restricts Legionella pneumophila Infection , 2009, PLoS pathogens.

[25]  F. Martinon,et al.  The inflammasomes: guardians of the body. , 2009, Annual review of immunology.

[26]  C.,et al.  processing and release of IL-1 Differential requirement for the activation of the inflammasome for , 2009 .

[27]  G. Superti-Furga,et al.  An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome , 2009, Nature Immunology.

[28]  Jasmyn A. Dunn,et al.  HIN-200 Proteins Regulate Caspase Activation in Response to Foreign Cytoplasmic DNA , 2009, Science.

[29]  M. Huang,et al.  Critical Role of Apoptotic Speck Protein Containing a Caspase Recruitment Domain (ASC) and NLRP3 in Causing Necrosis and ASC Speck Formation Induced by Porphyromonas gingivalis in Human Cells1 , 2009, The Journal of Immunology.

[30]  F. Sutterwala,et al.  Sensing pathogens and danger signals by the inflammasome. , 2009, Current opinion in immunology.

[31]  E. Alnemri,et al.  AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA , 2009, Nature.

[32]  Daniel R. Caffrey,et al.  AIM2 recognizes cytosolic dsDNA and forms a caspase-1 activating inflammasome with ASC , 2009, Nature.

[33]  Ruslan Medzhitov,et al.  Pattern recognition receptors and control of adaptive immunity , 2009, Immunological reviews.

[34]  L. Santambrogio,et al.  Anthrax Lethal Toxin Triggers the Formation of a Membrane-Associated Inflammasome Complex in Murine Macrophages , 2009, Infection and Immunity.

[35]  R. Medzhitov,et al.  Toll-like receptors and cancer , 2009, Nature Reviews Cancer.

[36]  T. Vanden Berghe,et al.  Targeted Peptidecentric Proteomics Reveals Caspase-7 as a Substrate of the Caspase-1 Inflammasomes *S , 2008, Molecular & Cellular Proteomics.

[37]  Karan Sharma,et al.  Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells. , 2008, Immunity.

[38]  Shizuo Akira,et al.  Toll‐like Receptor and RIG‐1‐like Receptor Signaling , 2008, Annals of the New York Academy of Sciences.

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

[40]  E. Brown,et al.  ESX‐1‐dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infection , 2008, Cellular microbiology.

[41]  F. Meissner,et al.  Superoxide dismutase 1 regulates caspase-1 and endotoxic shock , 2008, Nature Immunology.

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

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

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

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

[46]  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.

[47]  V. Nizet,et al.  A Nod2–nalp1 Complex Mediates Caspase-1-dependent Il-1␤ Secretion in Response to Bacillus Anthracis Infection and Muramyl Dipeptide Nod2, a Nod-like Receptor (nlr), Is an Intracellular Sensor of Bacterial Muramyl Dipeptide (mdp) That Was Suggested to Promote Secretion of the Proinflammatory Cytokine , 2022 .

[48]  A. Aderem,et al.  Multiple Nod-Like Receptors Activate Caspase 1 during Listeria monocytogenes Infection12 , 2008, The Journal of Immunology.

[49]  A. Surprenant,et al.  P2X7 Receptor Differentially Couples to Distinct Release Pathways for IL-1β in Mouse Macrophage1 , 2008, The Journal of Immunology.

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

[51]  F. Sutterwala,et al.  Maturation modulates caspase‐1‐independent responses of dendritic cells to Anthrax Lethal Toxin , 2008, Cellular microbiology.

[52]  Ana M. Rojas,et al.  The Nod-Like Receptor (NLR) Family: A Tale of Similarities and Differences , 2008, PloS one.

[53]  B. Cookson,et al.  Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms , 2008, Proceedings of the National Academy of Sciences.

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

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

[56]  A. Aderem,et al.  Pseudomonas aeruginosa activates caspase 1 through Ipaf , 2008, Proceedings of the National Academy of Sciences.

[57]  H. Takada,et al.  Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients. , 2008, Blood.

[58]  G. Núñez,et al.  A role for Nod-like receptors in autophagy induced by Shigella infection , 2008, Autophagy.

[59]  S. Leppla,et al.  Anthrax lethal toxin‐induced inflammasome formation and caspase‐1 activation are late events dependent on ion fluxes and the proteasome , 2007, Cellular microbiology.

[60]  F. Sutterwala,et al.  Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome , 2007, The Journal of experimental medicine.

[61]  Yao-Hui Sun,et al.  Injection of Flagellin into the Host Cell Cytosol by Salmonella enterica Serotype Typhimurium* , 2007, Journal of Biological Chemistry.

[62]  Raynal C. Squires,et al.  Proteasomes Control Caspase-1 Activation in Anthrax Lethal Toxin-mediated Cell Killing* , 2007, Journal of Biological Chemistry.

[63]  Gabriel Núñez,et al.  Frontline : Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation , 2007 .

[64]  Ruth R. Montgomery,et al.  ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection1 , 2007, The Journal of Immunology.

[65]  R. Flavell,et al.  Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1/cryopyrin/NLRP3 and ASC. , 2007, Cell host & microbe.

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

[67]  C. Sasakawa,et al.  Differential Regulation of Caspase-1 Activation, Pyroptosis, and Autophagy via Ipaf and ASC in Shigella-Infected Macrophages , 2007, PLoS pathogens.

[68]  P. Vandenabeele,et al.  The Nod-Like Receptor Family Member Naip5/Birc1e Restricts Legionella pneumophila Growth Independently of Caspase-1 Activation1 , 2007, The Journal of Immunology.

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

[70]  S. Adachi,et al.  Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells. , 2007, Blood.

[71]  N. Volkmann,et al.  Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. , 2007, Molecular cell.

[72]  H. Forman,et al.  ATP Activates a Reactive Oxygen Species-dependent Oxidative Stress Response and Secretion of Proinflammatory Cytokines in Macrophages* , 2007, Journal of Biological Chemistry.

[73]  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.

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

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

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

[77]  L. O’Neill,et al.  TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. , 2006, Trends in immunology.

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

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

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

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

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

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

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

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

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

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

[88]  A. Shaw,et al.  Triggering TLR signaling in vaccination. , 2006, Trends in immunology.

[89]  J. Cedarbaum Survival , 2004 .

[90]  V. Dixit,et al.  Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf , 2004, Nature.

[91]  M. Endrizzi,et al.  Naip5 Affects Host Susceptibility to the Intracellular Pathogen Legionella pneumophila , 2003, Current Biology.

[92]  P. Gros,et al.  Birc1e is the gene within the Lgn1 locus associated with resistance to Legionella pneumophila , 2003, Nature Genetics.

[93]  F. Martinon,et al.  The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. , 2002, Molecular cell.

[94]  W. Dietrich,et al.  High-resolution genetic and physical map of the Lgn1 interval in C57BL/6J implicates Naip2 or Naip5 in Legionella pneumophila pathogenesis. , 2000, Genome research.

[95]  H. S. Wolff,et al.  iRun: Horizontal and Vertical Shape of a Region-Based Graph Compression , 2022, Sensors.