Cellular Innate Immunity: An Old Game with New Players

Innate immunity is a rapidly evolving field with novel cell types and molecular pathways being discovered and paradigms changing continuously. Innate and adaptive immune responses are traditionally viewed as separate from each other, but emerging evidence suggests that they overlap and mutually interact. Recently discovered cell types, particularly innate lymphoid cells and myeloid-derived suppressor cells, are gaining increasing attention. Here, we summarize and highlight current concepts in the field, focusing on innate immune cells as well as the inflammasome and DNA sensing which appear to be critical for the activation and orchestration of innate immunity, and may provide novel therapeutic opportunities for treating autoimmune, autoinflammatory, and infectious diseases.

[1]  O. Nureki,et al.  Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. , 2017, Annual review of biochemistry.

[2]  A. Diefenbach,et al.  Innate lymphoid cells, precursors and plasticity. , 2016, Immunology letters.

[3]  D. Xia,et al.  Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome. , 2016, Immunity.

[4]  R. Xavier,et al.  Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages , 2016, Cell.

[5]  D. Underhill,et al.  Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan , 2016, Cell.

[6]  F. Takei,et al.  Allergen-Experienced Group 2 Innate Lymphoid Cells Acquire Memory-like Properties and Enhance Allergic Lung Inflammation. , 2016, Immunity.

[7]  J. Rathmell,et al.  A guide to immunometabolism for immunologists , 2016, Nature Reviews Immunology.

[8]  Peter J. Murray,et al.  Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards , 2016, Nature Communications.

[9]  T. Lämmermann,et al.  In the eye of the neutrophil swarm—navigation signals that bring neutrophils together in inflamed and infected tissues , 2016, Journal of leukocyte biology.

[10]  J. O’Shea,et al.  Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality , 2016, Cell.

[11]  K. Fitzgerald,et al.  Inflammasome Complexes: Emerging Mechanisms and Effector Functions , 2016, Cell.

[12]  N. Borregaard,et al.  Neutrophil extracellular traps - the dark side of neutrophils. , 2016, The Journal of clinical investigation.

[13]  B. Becher,et al.  NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22. , 2016, The Journal of clinical investigation.

[14]  D. Kasper,et al.  How colonization by microbiota in early life shapes the immune system , 2016, Science.

[15]  R. Xavier,et al.  Trained immunity: A program of innate immune memory in health and disease , 2016, Science.

[16]  P. Kubes,et al.  A Reservoir of Mature Cavity Macrophages that Can Rapidly Invade Visceral Organs to Affect Tissue Repair , 2016, Cell.

[17]  T. Gebhardt,et al.  Parallels and differences between innate and adaptive lymphocytes , 2016, Nature Immunology.

[18]  Y. Saeys,et al.  Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages. , 2016, Immunity.

[19]  Jonathan L. Schmid-Burgk,et al.  Human Monocytes Engage an Alternative Inflammasome Pathway. , 2016, Immunity.

[20]  A. Peschel,et al.  Myeloid-Derived Suppressor Cells in Bacterial Infections , 2016, Front. Cell. Infect. Microbiol..

[21]  G. Dubyak,et al.  T cell–intrinsic ASC critically promotes TH17-mediated experimental autoimmune encephalomyelitis , 2016, Nature Immunology.

[22]  E. Segal,et al.  Talking about cross-talk: the immune system and the microbiome , 2016, Genome Biology.

[23]  F. Ginhoux,et al.  Tissue-Resident Macrophage Ontogeny and Homeostasis. , 2016, Immunity.

[24]  T. Wynn,et al.  Macrophages in Tissue Repair, Regeneration, and Fibrosis. , 2016, Immunity.

[25]  Shuzhao Li,et al.  The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation , 2016, Nature.

[26]  B. Ye,et al.  Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity , 2016, Nature Immunology.

[27]  M. Kaplan,et al.  At the Bench: Neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases , 2016, Journal of leukocyte biology.

[28]  L. Crofford,et al.  At the Bedside: Neutrophil extracellular traps (NETs) as targets for biomarkers and therapies in autoimmune diseases , 2016, Journal of leukocyte biology.

[29]  J. Faith,et al.  Microbiota regulate the ability of lung dendritic cells to induce IgA class-switch recombination and generate protective gastrointestinal immune responses , 2016, The Journal of experimental medicine.

[30]  G. Núñez,et al.  Nek7 is an essential mediator of NLRP3 activation downstream of potassium efflux , 2016, Nature.

[31]  N. Kato,et al.  The cyclic GMP‐AMP synthetase–STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly , 2016, The FEBS journal.

[32]  Yves Levy,et al.  In vivo imaging of inflammasome activation reveals a subcapsular macrophage burst response that mobilizes innate and adaptive immunity , 2015, Nature Medicine.

[33]  C. Glass,et al.  Molecular control of activation and priming in macrophages , 2015, Nature Immunology.

[34]  R. Medzhitov,et al.  Tissue biology perspective on macrophages , 2015, Nature Immunology.

[35]  F. Geissmann,et al.  The development and maintenance of resident macrophages , 2015, Nature Immunology.

[36]  Si Ming Man,et al.  Converging roles of caspases in inflammasome activation, cell death and innate immunity , 2015, Nature Reviews Immunology.

[37]  R. Locksley,et al.  Tuft-cell-derived IL-25 regulates an intestinal ILC2–epithelial response circuit , 2015, Nature.

[38]  R. Jenq,et al.  Interleukin-22 Promotes Intestinal Stem Cell-Mediated Epithelial Regeneration , 2015, Nature.

[39]  Eric G. Pamer,et al.  From Hype to Hope: The Gut Microbiota in Enteric Infectious Disease , 2015, Cell.

[40]  T. Betsuyaku,et al.  Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses , 2015, Nature Immunology.

[41]  A. Rudensky,et al.  Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs , 2015, Science.

[42]  C. Sasakawa,et al.  Molecular mechanisms regulating NLRP3 inflammasome activation , 2015, Cellular and Molecular Immunology.

[43]  W. Shi,et al.  Complementarity and redundancy of IL-22-producing innate lymphoid cells , 2015, Nature Immunology.

[44]  Sara Omenetti,et al.  Cross-talk between type 3 innate lymphoid cells and the gut microbiota in inflammatory bowel disease , 2015, Current opinion in gastroenterology.

[45]  L. Joosten,et al.  Trained immunity: A smart way to enhance innate immune defence. , 2015, Molecular immunology.

[46]  S. Mazmanian,et al.  Gut biogeography of the bacterial microbiota , 2015, Nature Reviews Microbiology.

[47]  Jae U. Jung,et al.  Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway. , 2015, Cell reports.

[48]  A. McKenzie,et al.  Group 2 innate lymphoid cells license dendritic cells to potentiate memory T helper 2 cell responses , 2015, Nature Immunology.

[49]  S. Kummerfeld,et al.  Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling , 2015, Nature.

[50]  T. Cai,et al.  Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death , 2015, Nature.

[51]  Zhijian J. Chen,et al.  Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases , 2015, Proceedings of the National Academy of Sciences.

[52]  G. Kroemer,et al.  Transmission of innate immune signaling by packaging of cGAMP in viral particles , 2015, Science.

[53]  P. Borrow,et al.  Viruses transfer the antiviral second messenger cGAMP between cells , 2015, Science.

[54]  F. Neipel,et al.  Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein. , 2015, Cell host & microbe.

[55]  Elizabeth E Gray,et al.  Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1-Deficient Mouse Model of Aicardi–Goutières Syndrome , 2015, The Journal of Immunology.

[56]  L. Gregory,et al.  Pulmonary macrophages: key players in the innate defence of the airways , 2015, Thorax.

[57]  U. Yrlid,et al.  MyD88 Signaling Regulates Steady-State Migration of Intestinal CD103+ Dendritic Cells Independently of TNF-α and the Gut Microbiota , 2015, The Journal of Immunology.

[58]  J. Faith,et al.  Neutrophil ageing is regulated by the microbiome , 2015, Nature.

[59]  M. Fischbach,et al.  Small molecules from the human microbiota , 2015, Science.

[60]  Haitao Guo,et al.  Inflammasomes: mechanism of action, role in disease, and therapeutics , 2015, Nature Medicine.

[61]  B. Ryffel,et al.  The receptor NLRP3 is a transcriptional regulator of TH2 differentiation , 2015, Nature Immunology.

[62]  Nicolas Serafini,et al.  Transcriptional regulation of innate lymphoid cell fate , 2015, Nature Reviews Immunology.

[63]  R. Morita,et al.  Bruton's tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury , 2015, Nature Communications.

[64]  H. Virgin,et al.  The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy. , 2015, Cell host & microbe.

[65]  Zhijian J. Chen,et al.  Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis. , 2015, Cell host & microbe.

[66]  Y. Crow,et al.  Aicardi–Goutières syndrome and the type I interferonopathies , 2015, Nature Reviews Immunology.

[67]  M. Farrar,et al.  Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria–specific CD4+ T cells , 2015, Science.

[68]  M. Colonna,et al.  INNATE LYMPHOID CELLS Innate lymphoid cells : A new paradigm in immunology , 2018 .

[69]  J. Kuemmerle-Deschner.  CAPS — pathogenesis, presentation and treatment of an autoinflammatory disease , 2015, Seminars in Immunopathology.

[70]  T. Kanneganti.  The inflammasome: firing up innate immunity , 2015, Immunological reviews.

[71]  B. Kee,et al.  Innate Lymphoid Cells Control Early Colonization Resistance against Intestinal Pathogens through ID2-Dependent Regulation of the Microbiota. , 2015, Immunity.

[72]  J. Curtis,et al.  Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling , 2015, The Journal of experimental medicine.

[73]  L. Bosurgi,et al.  TAM receptor signaling in immune homeostasis. , 2015, Annual review of immunology.

[74]  E. Pamer,et al.  Microbiota-mediated inflammation and antimicrobial defense in the intestine. , 2015, Annual review of immunology.

[75]  D. Monack,et al.  This information is current as Infection Francisella I IFNs in Response to cGAS and Ifi 204 Cooperate To Produce Type , 2015 .

[76]  N. Grishin,et al.  Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation , 2015, Science.

[77]  O. Mandelboim,et al.  NK cells link obesity-induced adipose stress to inflammation and insulin resistance , 2015, Nature Immunology.

[78]  Dirk Roos,et al.  Neutrophils: Between Host Defence, Immune Modulation, and Tissue Injury , 2015, PLoS pathogens.

[79]  K. Schroder,et al.  A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases , 2015, Nature Medicine.

[80]  W. Bishai,et al.  A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis , 2015, Nature Medicine.

[81]  C. Mohan,et al.  Suppression of systemic autoimmunity by the innate immune adaptor STING , 2015, Proceedings of the National Academy of Sciences.

[82]  B. Schittek,et al.  The secrets of dermcidin action. , 2015, International journal of medical microbiology : IJMM.

[83]  A. Luster,et al.  The chemokine system in innate immunity. , 2015, Cold Spring Harbor perspectives in biology.

[84]  R. Locksley,et al.  Activated Type 2 Innate Lymphoid Cells Regulate Beige Fat Biogenesis , 2015, Cell.

[85]  R. Maizels,et al.  CCR7-dependent trafficking of RORγ+ ILCs creates a unique microenvironment within mucosal draining lymph nodes , 2015, Nature Communications.

[86]  S. Koyasu,et al.  Innate lymphoid cells, possible interaction with microbiota , 2014, Seminars in Immunopathology.

[87]  I. Amit,et al.  Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment , 2014, Cell.

[88]  Lanjuan Li,et al.  Natural killer T cells play a necessary role in modulating of immune-mediated liver injury by gut microbiota , 2014, Scientific Reports.

[89]  N. Salzman.  The role of the microbiome in immune cell development. , 2014, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[90]  Hergen Spits,et al.  Innate lymphoid cells in inflammation and immunity. , 2014, Immunity.

[91]  M. Colonna,et al.  Development, differentiation, and diversity of innate lymphoid cells. , 2014, Immunity.

[92]  Q. Wang,et al.  Neutrophils sense microbial size and selectively release neutrophil extracellular traps in response to large pathogens , 2014, Nature Immunology.

[93]  V. Lupashin,et al.  The DNA Sensor, Cyclic GMP–AMP Synthase, Is Essential for Induction of IFN-β during Chlamydia trachomatis Infection , 2014, The Journal of Immunology.

[94]  G. Ogg,et al.  MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4+ T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion , 2014, Immunity.

[95]  A. Rudensky,et al.  Interactions between innate and adaptive lymphocytes , 2014, Nature Reviews Immunology.

[96]  H. Jaspan,et al.  The Role of Myeloid-Derived Suppressor Cells in Immune Ontogeny , 2014, Front. Immunol..

[97]  K. Buchmann,et al.  Evolution of Innate Immunity: Clues from Invertebrates via Fish to Mammals , 2014, Front. Immunol..

[98]  P. Li,et al.  Inflammatory caspases are innate immune receptors for intracellular LPS , 2014, Nature.

[99]  T. Decker,et al.  Listeria monocytogenes induces IFNβ expression through an IFI16‐, cGAS‐ and STING‐dependent pathway , 2014, The EMBO journal.

[100]  V. Hornung,et al.  OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids , 2014, Nature Reviews Immunology.

[101]  E. Vigorito,et al.  Noncoding RNA and its associated proteins as regulatory elements of the immune system , 2014, Nature Immunology.

[102]  H. Deshmukh,et al.  The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice , 2014, Nature Medicine.

[103]  Henrique Veiga-Fernandes,et al.  Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages , 2014, Cell.

[104]  Zhijian J. Chen,et al.  Modified Vaccinia Virus Ankara Triggers Type I IFN Production in Murine Conventional Dendritic Cells via a cGAS/STING-Mediated Cytosolic DNA-Sensing Pathway , 2014, PLoS pathogens.

[105]  M. Hepworth,et al.  Regulation of the adaptive immune system by innate lymphoid cells. , 2014, Current opinion in immunology.

[106]  Y. Belkaid,et al.  Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis , 2014, Science.

[107]  A. Luster,et al.  Chemokines and chemokine receptors: positioning cells for host defense and immunity. , 2014, Annual review of immunology.

[108]  M. Gold,et al.  Group 2 Innate Lymphoid Cells Are Critical for the Initiation of Adaptive T Helper 2 Cell-Mediated Allergic Lung Inflammation , 2014, Immunity.

[109]  Katherine A. Fitzgerald,et al.  Unified Polymerization Mechanism for the Assembly of ASC-Dependent Inflammasomes , 2014, Cell.

[110]  G. Barber,et al.  Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-κB Activation through TBK1 , 2014, Journal of Virology.

[111]  Tom C. Freeman,et al.  Transcriptome-Based Network Analysis Reveals a Spectrum Model of Human Macrophage Activation , 2014, Immunity.

[112]  T. Hussell,et al.  Alveolar macrophages: plasticity in a tissue-specific context , 2014, Nature Reviews Immunology.

[113]  A. Prince,et al.  Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity , 2014, Nature.

[114]  Xin Geng,et al.  Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection , 2013, Nature.

[115]  C. Kao,et al.  Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization. , 2013, Immunity.

[116]  R. Hancock,et al.  Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. , 2013, Nature chemical biology.

[117]  E. Lam,et al.  Adenovirus Detection by the cGAS/STING/TBK1 DNA Sensing Cascade , 2013, Journal of Virology.

[118]  P. Kubes,et al.  NETosis: how vital is it? , 2013, Blood.

[119]  Jonathan L. Schmid-Burgk,et al.  Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP , 2013, Nature.

[120]  Zhijian J. Chen,et al.  Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects , 2013, Science.

[121]  M. T. Wong,et al.  Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4 , 2013, Science.

[122]  John D Lambris,et al.  Complement modulates the cutaneous microbiome and inflammatory milieu , 2013, Proceedings of the National Academy of Sciences.

[123]  S. Thiel,et al.  Humoral Pattern Recognition and the Complement System , 2013, Scandinavian journal of immunology.

[124]  G. Young,et al.  Counterpoise between the microbiome, host immune activation and pathology. , 2013, Current opinion in immunology.

[125]  Zhijian J. Chen,et al.  Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. , 2013, Molecules and Cells.

[126]  A. Winoto,et al.  Commensal microbiota are required for systemic inflammation triggered by necrotic dendritic cells. , 2013, Cell reports.

[127]  F. Bushman,et al.  Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance. , 2013, Immunity.

[128]  A. Rudensky,et al.  IL-2–dependent adaptive control of NK cell homeostasis , 2013, The Journal of experimental medicine.

[129]  S. Lang,et al.  The kinship of neutrophils and granulocytic myeloid-derived suppressor cells in cancer: cousins, siblings or twins? , 2013, Seminars in cancer biology.

[130]  V. Hornung,et al.  Structural mechanism of cytosolic DNA sensing by cGAS , 2013, Nature.

[131]  R. Vance,et al.  The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. , 2013, Cell reports.

[132]  V. Hornung,et al.  cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING , 2013, Nature.

[133]  Bastian R. Angermann,et al.  Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo , 2013, Nature.

[134]  Roger A. Jones,et al.  Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase , 2013, Cell.

[135]  F. Bushman,et al.  Innate lymphoid cells regulate CD4+ T cell responses to intestinal commensal bacteria , 2013, Nature.

[136]  A. Jayaraman,et al.  A role for microbiota metabolites in generation of mucosal dendritic cells (P3160) , 2013, Journal of Immunology.

[137]  Zbigniew Mikulski,et al.  Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance , 2013, The Journal of experimental medicine.

[138]  S. Singhal,et al.  Myeloid derived suppressor cells , 2013, Oncoimmunology.

[139]  Liang Zheng,et al.  Succinate is an inflammatory signal that induces IL-1β through HIF-1α , 2013, Nature.

[140]  R. Locksley,et al.  Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages , 2013, The Journal of experimental medicine.

[141]  P. Kubes,et al.  Neutrophil recruitment and function in health and inflammation , 2013, Nature Reviews Immunology.

[142]  Zhijian J. Chen,et al.  Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway , 2013, Science.

[143]  Sangdun Choi,et al.  Negative regulatory approaches to the attenuation of Toll-like receptor signaling , 2013, Experimental & Molecular Medicine.

[144]  D. Wagner,et al.  Neutrophil extracellular traps , 2013, Oncoimmunology.

[145]  Junying Yuan,et al.  Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity. , 2013, Molecular cell.

[146]  A. Sica,et al.  Macrophage plasticity and polarization in tissue repair and remodelling , 2013, The Journal of pathology.

[147]  R. Germain,et al.  The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP , 2012, Nature.

[148]  G. Barber,et al.  STING manifests self DNA-dependent inflammatory disease , 2012, Proceedings of the National Academy of Sciences.

[149]  B. Morgan,et al.  Complement dysregulation and disease: from genes and proteins to diagnostics and drugs. , 2012, Immunobiology.

[150]  L. Vieira,et al.  Absence of Microbiota Impairs Macrophage Microbicide Activity and Production of Nitric Oxide and Reative Species of Oxygen , 2012 .

[151]  D. Artis,et al.  Innate lymphoid cell interactions with microbiota: implications for intestinal health and disease. , 2012, Immunity.

[152]  Ronald N. Germain,et al.  A Spatially-Organized Multicellular Innate Immune Response in Lymph Nodes Limits Systemic Pathogen Spread , 2012, Cell.

[153]  Natalie A. Roberts,et al.  Cutting Edge: Lymphoid Tissue Inducer Cells Maintain Memory CD4 T Cells within Secondary Lymphoid Tissue , 2012, The Journal of Immunology.

[154]  A. Peschel,et al.  Anuclear neutrophils keep hunting , 2012, Nature Medicine.

[155]  M. Asaduzzaman,et al.  Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo , 2012, Nature Medicine.

[156]  M. Carroll,et al.  Regulation of humoral immunity by complement. , 2012, Immunity.

[157]  K. Tracey,et al.  Alarmins: awaiting a clinical response. , 2012, The Journal of clinical investigation.

[158]  P. Staeheli,et al.  Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota. , 2012, Immunity.

[159]  S. Lang,et al.  Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology , 2012, Cancer Immunology, Immunotherapy.

[160]  C. Bryant,et al.  Mice, men and the relatives: cross-species studies underpin innate immunity , 2012, Open Biology.

[161]  B. Schittek.  The Multiple Facets of Dermcidin in Cell Survival and Host Defense , 2012, Journal of Innate Immunity.

[162]  B. Ahmer,et al.  The intestinal microbiota are necessary for stressor-induced enhancement of splenic macrophage microbicidal activity , 2012, Brain, Behavior, and Immunity.

[163]  Alberto Mantovani,et al.  Macrophage plasticity and polarization: in vivo veritas. , 2012, The Journal of clinical investigation.

[164]  D. Stetson,et al.  Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. , 2012, Immunity.

[165]  Jinfeng Liu,et al.  Non-canonical inflammasome activation targets caspase-11 , 2011, Nature.

[166]  S. Galli,et al.  Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils , 2011, Nature Immunology.

[167]  David Artis,et al.  Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus , 2011, Nature Immunology.

[168]  E. Pamer,et al.  Role of the commensal microbiota in normal and pathogenic host immune responses. , 2011, Cell host & microbe.

[169]  T. Wynn,et al.  Protective and pathogenic functions of macrophage subsets , 2011, Nature Reviews Immunology.

[170]  Yong‐jun Liu,et al.  The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells , 2011, Nature Immunology.

[171]  S. Ng,et al.  Relationship between human intestinal dendritic cells, gut microbiota, and disease activity in Crohn's disease , 2011, Inflammatory bowel diseases.

[172]  T. Fujita,et al.  RIG‐I‐like receptors: cytoplasmic sensors for non‐self RNA , 2011, Immunological reviews.

[173]  M. Manns,et al.  Myeloid derived suppressor cells in human diseases. , 2011, International immunopharmacology.

[174]  J. Gordon,et al.  Human nutrition, the gut microbiome and the immune system , 2011, Nature.

[175]  F. Finkelman,et al.  Local Macrophage Proliferation, Rather than Recruitment from the Blood, Is a Signature of TH2 Inflammation , 2011, Science.

[176]  S. Akira,et al.  Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. , 2011, Immunity.

[177]  V. Hornung,et al.  Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions , 2011, Science Translational Medicine.

[178]  B. Amulic,et al.  Neutrophil extracellular traps , 2011, Current Biology.

[179]  N. Salzman,et al.  Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis , 2011, Nature Reviews Microbiology.

[180]  T. Wynn,et al.  Obstacles and opportunities for understanding macrophage polarization , 2011, Journal of leukocyte biology.

[181]  G. Eberl,et al.  RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota , 2011, Nature Immunology.

[182]  S. Gordon,et al.  Innate immunity to intracellular pathogens: macrophage receptors and responses to microbial entry , 2011, Immunological reviews.

[183]  M. Surette,et al.  A Novel Mechanism of Rapid Nuclear Neutrophil Extracellular Trap Formation in Response to Staphylococcus aureus , 2010, The Journal of Immunology.

[184]  A. Mantovani,et al.  The growing diversity and spectrum of action of myeloid‐derived suppressor cells , 2010, European journal of immunology.

[185]  A. Bowie,et al.  IFI16 is an innate immune sensor for intracellular DNA , 2010, Nature Immunology.

[186]  Je-in Youn,et al.  The biology of myeloid‐derived suppressor cells: The blessing and the curse of morphological and functional heterogeneity , 2010, European journal of immunology.

[187]  J. Borghans,et al.  In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. , 2010, Blood.

[188]  D. Portnoy,et al.  c-di-AMP Secreted by Intracellular Listeria monocytogenes Activates a Host Type I Interferon Response , 2010, Science.

[189]  S. Akira,et al.  The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors , 2010, Nature Immunology.

[190]  Maureen A. McGargill,et al.  Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis. , 2010, Journal of immunology.

[191]  V. Hornung,et al.  Intracellular DNA recognition , 2010, Nature Reviews Immunology.

[192]  H. Simon,et al.  Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps , 2009, Cell Death and Differentiation.

[193]  G. de la Rosa,et al.  Alarmins link neutrophils and dendritic cells. , 2009, Trends in immunology.

[194]  G. Barber,et al.  STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity , 2009, Nature.

[195]  S. Plevy,et al.  S1719 Macrophage Tolerance to the Enteric Microbiota Is Mediated By IL-10 At the Chromatin Level , 2009 .

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

[197]  D. Hume,et al.  CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation , 2009, The Journal of experimental medicine.

[198]  Srinivas Nagaraj,et al.  Myeloid-derived suppressor cells as regulators of the immune system , 2009, Nature Reviews Immunology.

[199]  R. Gallo,et al.  AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. , 2009, Trends in immunology.

[200]  A. Zychlinsky,et al.  Mouse Neutrophil Extracellular Traps in Microbial Infections , 2009, Journal of Innate Immunity.

[201]  B. Cookson,et al.  Pyroptosis: host cell death and inflammation , 2009, Nature Reviews Microbiology.

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

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

[204]  Joseph C. Sun,et al.  Adaptive Immune Features of Natural Killer Cells , 2009, Nature.

[205]  J. Elias,et al.  Chitin regulation of immune responses: an old molecule with new roles. , 2008, Current opinion in immunology.

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

[207]  J. Borneman,et al.  Systemic Control of Plasmacytoid Dendritic Cells by CD8+ T Cells and Commensal Microbiota1 , 2008, The Journal of Immunology.

[208]  Volker Brinkmann,et al.  Beneficial suicide: why neutrophils die to make NETs , 2007, Nature Reviews Microbiology.

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

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

[211]  N. Salzman,et al.  Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa. , 2007, Seminars in immunology.

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

[213]  U. V. Andrian,et al.  T cell– and B cell–independent adaptive immunity mediated by natural killer cells , 2006, Nature Immunology.

[214]  H. Reinecker,et al.  Dendritic cells in the recognition of intestinal microbiota , 2006, Cellular microbiology.

[215]  M. Shlomchik.  Faculty Opinions recommendation of Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA. , 2005 .

[216]  S. Gordon,et al.  The role of scavenger receptors in pathogen recognition and innate immunity. , 2004, Immunobiology.

[217]  D. Barnes,et al.  Gene-Targeted Mice Lacking the Trex1 (DNase III) 3′→5′ DNA Exonuclease Develop Inflammatory Myocarditis , 2004, Molecular and Cellular Biology.

[218]  A. Zychlinsky,et al.  Neutrophil Extracellular Traps Kill Bacteria , 2004, Science.

[219]  S. Nagata,et al.  Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. , 2001, Science.

[220]  B. Rollins,et al.  Chemokines and disease , 2001, Nature Immunology.

[221]  J. Falloon,et al.  Neutrophil granules in health and disease. , 1986, The Journal of allergy and clinical immunology.

[222]  B. Becher,et al.  NLRP 3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN 22 , 2018 .

[223]  M. Kaplan,et al.  Disentangling the role of neutrophil extracellular traps in rheumatic diseases. , 2017, Current opinion in rheumatology.

[224]  T. Kanneganti,et al.  Novel roles for caspase-8 in IL-1β and inflammasome regulation. , 2015, The American journal of pathology.

[225]  D. Hume,et al.  Edinburgh Research Explorer common macrophage/DC precursors and the role of CX(3)CR1 in their response to inflammation , 2009 .

[226]  S Gordon,et al.  Macrophage receptors and immune recognition. , 2005, Annual review of immunology.

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