BRUCE A BEUTLER

Summary

Affiliation: The Scripps Research Institute
Country: USA

Publications

  1. pmc Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis
    Karine Crozat
    The Scripps Research Institute TSRI, La Jolla, CA 92037, USA
    J Exp Med 204:853-63. 2007
  2. pmc An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence
    Michael Berger
    Department of Genetics, The Scripps Research Institute, La Jolla, California, USA
    Nat Immunol 11:335-43. 2010
  3. pmc The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow
    Owen M Siggs
    Department of Genetics, The Scripps Research Institute, La Jolla, California, USA
    Nat Immunol 12:434-40. 2011
  4. ncbi Genetic analysis of resistance to viral infection
    Bruce Beutler
    Department of Genetics, The Scripps Research Institute, IMM 3 1, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Immunol 7:753-66. 2007
  5. ncbi Forward genetic dissection of afferent immunity: the role of TIR adapter proteins in innate and adaptive immune responses
    Bruce Beutler
    The Scripps Research Institute, La Jolla, CA 92037, USA
    C R Biol 327:571-80. 2004
  6. ncbi Inferences, questions and possibilities in Toll-like receptor signalling
    Bruce Beutler
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Nature 430:257-63. 2004
  7. ncbi Neo-ligands for innate immune receptors and the etiology of sterile inflammatory disease
    Bruce Beutler
    The Scripps Research Institute, La Jolla, CA, USA
    Immunol Rev 220:113-28. 2007
  8. ncbi Precis on forward genetics in mice
    Bruce Beutler
    Department of Genetics, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Immunol 8:659-64. 2007
  9. ncbi Genetic analysis of innate immunity: TIR adapter proteins in innate and adaptive immune responses
    Bruce Beutler
    Department of Immunology, The Scripps Research Institute, IMM 31, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Microbes Infect 6:1374-81. 2004
  10. ncbi Genetic dissection of innate immunity to infection: the mouse cytomegalovirus model
    Bruce Beutler
    Department of Immunology and Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Immunol 17:36-43. 2005

Research Grants

  1. Mutagenetic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2007
  2. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2005
  3. TLR4 AS AN LPS SENSOR AND SUSCEPTIBILITY LOCUS
    Bruce Beutler; Fiscal Year: 2003
  4. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2003
  5. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2003
  6. TLR4 AS AN LPS SENSOR AND SUSCEPTIBILITY LOCUS
    Bruce Beutler; Fiscal Year: 2001
  7. TLR4 AS AN LPS SENSOR AND SUSCEPTIBILITY LOCUS
    Bruce Beutler; Fiscal Year: 2002
  8. TLR4 as an LPS sendor and susceptibility locus
    Bruce Beutler; Fiscal Year: 2007
  9. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2006
  10. Forward Genetic Analysis of the Innate Immune Contribution to MCMV Resistance
    Bruce Beutler; Fiscal Year: 2006

Detail Information

Publications76

  1. pmc Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis
    Karine Crozat
    The Scripps Research Institute TSRI, La Jolla, CA 92037, USA
    J Exp Med 204:853-63. 2007
    ..In contrast, neither Listeria monocytogenes nor MCMV induces the syndrome. In mice, the HLH phenotype is conditional, which suggests the existence of a specific infectious trigger of FHL3 in humans...
  2. pmc An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence
    Michael Berger
    Department of Genetics, The Scripps Research Institute, La Jolla, California, USA
    Nat Immunol 11:335-43. 2010
    ..Our findings identify a physiological role for Slfn2 in the defense against pathogens through the regulation of quiescence in T cells and monocytes...
  3. pmc The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow
    Owen M Siggs
    Department of Genetics, The Scripps Research Institute, La Jolla, California, USA
    Nat Immunol 12:434-40. 2011
    ..Our data establish an essential, cell-autonomous and context-sensitive function for ATP11C, a putative aminophospholipid flippase, in B cell development...
  4. ncbi Genetic analysis of resistance to viral infection
    Bruce Beutler
    Department of Genetics, The Scripps Research Institute, IMM 3 1, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Immunol 7:753-66. 2007
    ..Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament...
  5. ncbi Forward genetic dissection of afferent immunity: the role of TIR adapter proteins in innate and adaptive immune responses
    Bruce Beutler
    The Scripps Research Institute, La Jolla, CA 92037, USA
    C R Biol 327:571-80. 2004
    ..Forward genetic analysis has revealed that this upregulation depends upon an adapter encoded by a locus known as Lps2, and upon type I interferon receptor signaling...
  6. ncbi Inferences, questions and possibilities in Toll-like receptor signalling
    Bruce Beutler
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Nature 430:257-63. 2004
    ..And it now seems that many inflammatory processes, both sterile and infectious, may depend on TLR signalling. We are in a good position to apply our understanding of TLR signalling to a range of challenges in immunology and medicine...
  7. ncbi Neo-ligands for innate immune receptors and the etiology of sterile inflammatory disease
    Bruce Beutler
    The Scripps Research Institute, La Jolla, CA, USA
    Immunol Rev 220:113-28. 2007
    ..It explains sterile inflammatory diseases as conditions in which aberrant immune signaling is caused by proteome encroachment upon the ligand-recognition space over which the innate immune system stands guard...
  8. ncbi Precis on forward genetics in mice
    Bruce Beutler
    Department of Genetics, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Immunol 8:659-64. 2007
  9. ncbi Genetic analysis of innate immunity: TIR adapter proteins in innate and adaptive immune responses
    Bruce Beutler
    Department of Immunology, The Scripps Research Institute, IMM 31, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Microbes Infect 6:1374-81. 2004
    ..Other key innate immunity proteins have been disclosed by germline mutagenesis, and are discussed in the present review...
  10. ncbi Genetic dissection of innate immunity to infection: the mouse cytomegalovirus model
    Bruce Beutler
    Department of Immunology and Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Immunol 17:36-43. 2005
    ....
  11. ncbi The sole gateway to endotoxin response: how LPS was identified as Tlr4, and its role in innate immunity
    B Beutler
    The Scripps Research Institute, La Jolla, CA 92027, USA
    Drug Metab Dispos 29:474-8. 2001
    ..Some such receptors may also play developmental roles. The mutational deletion of Tlr genes alone and in combination with one another may help to establish the functions of each member of this newly emergent family of proteins...
  12. ncbi Genetic analysis of innate resistance to mouse cytomegalovirus (MCMV)
    Bruce Beutler
    The Scripps Research Institute, 10550 N Torrey Pines Road, IMM 31, La Jolla, CA 92037, USA
    Brief Funct Genomic Proteomic 4:203-13. 2005
    ..The forward genetics approach offers an excellent opportunity to identify many of the key components of the innate immune system...
  13. ncbi TLR signaling pathways: opportunities for activation and blockade in pursuit of therapy
    K Hoebe
    Department of Immunology, IMM 31, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037 USA
    Curr Pharm Des 12:4123-34. 2006
    ..Classical and reverse genetic analyses offer insight into the possibilities that exist, and point to specific checkpoints within signaling pathways at which modulation might normally be imposed...
  14. ncbi Analysis of the MCMV resistome by ENU mutagenesis
    Karine Crozat
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Mamm Genome 17:398-406. 2006
    ....
  15. ncbi Genetic analysis of innate immunity: identification and function of the TIR adapter proteins
    Bruce Beutler
    Scripps Research Institute, Department of Immunology, IMM 31, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Adv Exp Med Biol 560:29-39. 2005
    ..Other key innate immunity genes have also been disclosed by germline mutagenesis, and are discussed in the present review...
  16. pmc New frontiers in immunology. Workshop on the road ahead: future directions in fundamental and clinical immunology
    Bruce Beutler
    Department of Immunology, IMM 31, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    EMBO Rep 6:620-3. 2005
  17. ncbi The Toll-like receptors: analysis by forward genetic methods
    Bruce Beutler
    The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA
    Immunogenetics 57:385-92. 2005
    ..These include the development of fever, shock, and tissue injury, but also the activation of innate and adaptive effector mechanisms that lead to the elimination of microbes...
  18. ncbi Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large
    Bruce Beutler
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    Annu Rev Immunol 24:353-89. 2006
    ..A still broader genetic screen--one that detects all mutations that compromise survival during infection--is permitting fresh insight into the number and types of proteins that mammals use to defend themselves against microbes...
  19. ncbi Toll-like receptors and their place in immunology. Where does the immune response to infection begin?
    Bruce Beutler
    The Scripps Research Institute, Department of Immunology, IMM 3110550, N Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Immunol 4:498. 2004
  20. ncbi The forward genetic dissection of afferent innate immunity
    B Beutler
    Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA
    Curr Top Microbiol Immunol 321:3-26. 2008
    ..As discussed here, mutagenesis has revealed proteins that participate in TLR signaling pathways, and informed our understanding of the subtleties of these molecules' structure and function...
  21. ncbi Innate immunity: an overview
    Bruce Beutler
    Department of Immunology, IMM 31, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Immunol 40:845-59. 2004
    ..This has opened the way to an understanding of innate immune sensing. The effector arm of innate immunity has also been tackled, largely though the use of biochemical methods...
  22. ncbi Sepsis and evolution of the innate immune response
    B Beutler
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Crit Care Med 29:S2-6; discussion S6-7. 2001
    ..To review the role of the Toll-like receptors (TLR) as the principal sensors used by the innate immune system in the context of the pathologic processes underlying sepsis and septic shock...
  23. ncbi Sepsis begins at the interface of pathogen and host
    B Beutler
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Biochem Soc Trans 29:853-9. 2001
    ..In mammals, proteins of this family are now known as Toll-like receptors. They represent a point of direct contact, and first contact, between a pathogen and the host immune system...
  24. ncbi Toll-like receptors: how they work and what they do
    Bruce Beutler
    Scripps Research Institute, La Jolla, California 92037, USA
    Curr Opin Hematol 9:2-10. 2002
    ..The sequence of events that led to the discovery of Toll-like receptor function carries an important lesson that should guide further analysis of the innate immune system...
  25. ncbi Endotoxin antagonism: conceptual basis and therapeutic potential
    Bruce Beutler
    The Scripps Research Institute, 10550 N, Torrey Pines Road, La Jolla, CA 92037, USA
    Expert Opin Ther Targets 6:147-58. 2002
    ..The question at hand has become a practical one: can this understanding be exploited to a therapeutic advantage?..
  26. ncbi Innate immune sensing of microbial infection: the mechanism and the therapeutic challenge
    B Beutler
    Scripps Research Institute, 10550 N Torrey Pines Road, IMM 31, La Jolla, CA 92037, USA
    Wien Med Wochenschr 152:547-51. 2002
    ..At the same time, it is known that TLRs are required to sense infection at its earliest stages, and thereby defeat it. The means to block TLR signal transduction is now at hand. Will this do good or harm?..
  27. ncbi LPS in microbial pathogenesis: promise and fulfilment
    Bruce Beutler
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Endotoxin Res 8:329-35. 2002
    ..Moreover, it has amalgamated many separate lines of inquiry, and focused attention on the how the innate immune system perceives infection...
  28. ncbi Innate immune responses to microbial poisons: discovery and function of the Toll-like receptors
    Bruce Beutler
    The Scripps Research Institute, Department of Immunology, La Jolla, California 92037, USA
    Annu Rev Pharmacol Toxicol 43:609-28. 2003
    ....
  29. ncbi Innate immune sensing and its roots: the story of endotoxin
    Bruce Beutler
    The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Rev Immunol 3:169-76. 2003
    ..The discovery of the host sensors--the Toll-like receptors--was rooted in chemical, biological and genetic analyses that centred on a bacterial poison, termed endotoxin...
  30. pmc Science review: key inflammatory and stress pathways in critical illness - the central role of the Toll-like receptors
    Bruce Beutler
    Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
    Crit Care 7:39-46. 2003
    ..The continued application of both forward and reverse genetic methods, in both mammals and insects, is steadily revealing the central biochemical events that occur during infection...
  31. doi How host defense is encoded in the mammalian genome
    Bruce Beutler
    Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mamm Genome 22:1-5. 2011
    ..Classical genetic studies opened and continue to pave the way to deep understanding of many issues in immunology...
  32. ncbi From phenomenon to phenotype and from phenotype to gene: forward genetics and the problem of sepsis
    Bruce Beutler
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    J Infect Dis 187:S321-6. 2003
    ..Which genes are involved in the pathogenesis of sepsis? As in the golden age of genetics, the answer requires the solution of phenotypic puzzles, which, in turn, requires the creation of phenotypes...
  33. pmc Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases
    Bruce Beutler
    Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA
    Immunol Rev 227:248-63. 2009
    ..We have also developed some insight into critical points at which feedback loops can be interrupted...
  34. ncbi How we detect microbes and respond to them: the Toll-like receptors and their transducers
    B Beutler
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Leukoc Biol 74:479-85. 2003
    ....
  35. ncbi Lps2 and signal transduction in sepsis: at the intersection of host responses to bacteria and viruses
    Bruce Beutler
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Scand J Infect Dis 35:563-7. 2003
    ..Positional cloning revealed that the TIR adapter protein Trif/Ticam-1 is structurally altered by the Lps2 mutation. This adapter is responsible for shared effects of responses to viral and bacterial pathogens...
  36. pmc TLRs and innate immunity
    BRUCE A BEUTLER
    Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood 113:1399-407. 2009
    ..Herein is a concise description of what has been learned about the Toll-like receptors, which play an essential part in the perception of microbes and shape the complex host responses that occur during infection...
  37. pmc Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells
    Yi Ting Koh
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 190:4982-90. 2013
    ..In particular, our findings suggest that targeting of NA-TLR signaling in B cells alone would be sufficient to specifically block production of a broad diversity of autoantibodies...
  38. pmc Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection
    Koichi Tabeta
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:3516-21. 2004
    ..The phenotypic effect of the Tlr9(CpG1) allele thus points to a critical role for TLR9 in viral sensing and identifies a vulnerable amino acid within the ectodomain of three TLR proteins, essential for a ligand response...
  39. ncbi Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways
    Kasper Hoebe
    The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Immunol 4:1223-9. 2003
    ..These findings show that UCM involves an autocrine or paracrine loop, and indicate that an alternative TLR3-independent, Trif-independent pathway contributes to dsRNA-induced UCM...
  40. ncbi Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway
    Philippe Georgel
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Virology 362:304-13. 2007
    ....
  41. ncbi CD14 is required for MyD88-independent LPS signaling
    Zhengfan Jiang
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Nat Immunol 6:565-70. 2005
    ..Thus, the TLR4-MD-2 complex receptor can function in two separate modes: one in which full signaling occurs and one limited to MyD88-dependent signaling...
  42. doi The Tpl2 mutation Sluggish impairs type I IFN production and increases susceptibility to group B streptococcal disease
    Nengming Xiao
    Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 183:7975-83. 2009
    ..Our data demonstrate that the encoded protein kinase Tpl2 plays an essential role in cell signaling in the immune response to certain pathogens...
  43. ncbi Enhanced antibacterial potential in UBP43-deficient mice against Salmonella typhimurium infection by up-regulating type I IFN signaling
    Keun Il Kim
    Departments of Molecular and Experimental Medicine and Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 175:847-54. 2005
    ..These results clearly demonstrate two aspects of IFN-signaling, a beneficial effect against pathogens but a detriment to the body without strict control...
  44. pmc Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling
    Amanda L Gavin
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037 USA
    Science 314:1936-8. 2006
    ..This may have important implications in the use and development of vaccine adjuvants...
  45. ncbi ATP-sensitive potassium channels mediate survival during infection in mammals and insects
    Ben Croker
    Department of Genetics, IMM 31, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Genet 39:1453-60. 2007
    ..Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors...
  46. ncbi Lps2: a new locus required for responses to lipopolysaccharide, revealed by germline mutagenesis and phenotypic screening
    Kasper Hoebe
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Endotoxin Res 9:250-5. 2003
    ..The Lps2 mutation does not preclude signaling initiated by peptidoglycan or unmethylated DNA. Hence, genetic data suggest that there is at least one 'missing' component of the LPS receptor complex that has yet to be found...
  47. ncbi Antagonism between MyD88- and TRIF-dependent signals in B7RP-1 up-regulation
    Zuping Zhou
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Eur J Immunol 35:1918-27. 2005
    ..These data indicate that Type I IFN play a dual role in the TLR-mediated expression of B7 costimulatory family members and suggest that they may act to limit B7RP-1 expression and thus limit signals derived from B7RP-1-ICOS interaction...
  48. pmc Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus
    Dwight H Kono
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:12061-6. 2009
    ..Importantly, this helps provide an explanation for the high frequency of anti-nucleic acid Abs in lupus-like systemic autoimmunity...
  49. ncbi CD36 is a sensor of diacylglycerides
    Kasper Hoebe
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nature 433:523-7. 2005
    ..Already known as a receptor for endogenous molecules, CD36 is also a selective and nonredundant sensor of microbial diacylglycerides that signal via the TLR2/6 heterodimer...
  50. ncbi The interface between innate and adaptive immunity
    Kasper Hoebe
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Immunol 5:971-4. 2004
    ..This focus analyzes some of the ways the innate immune system influences adaptive immune responses. Here the main principles and themes that govern this intricate relationship are discussed...
  51. ncbi PanR1, a dominant negative missense allele of the gene encoding TNF-alpha (Tnf), does not impair lymphoid development
    Sophie Rutschmann
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 176:7525-32. 2006
    ..However, PanR1 mutant mice show normal architecture of the spleen and Peyer's patches, suggesting that TNF is not essential for the formation of these lymphoid structures...
  52. pmc Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis
    Zhengfan Jiang
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 103:10961-6. 2006
    ..Moreover, MyD88 engages individual TLRs differently, suggesting the feasibility of selective pharmacologic TIR domain receptor blockade...
  53. doi Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice
    Michael J Barnes
    Department of Genetics, Scripps Research Institute, La Jolla, CA, USA
    J Immunol 184:3743-54. 2010
    ..These data establish Gimap5 as a key regulator of hematopoietic integrity and lymphocyte homeostasis...
  54. pmc Metabolic characterization of a mouse deficient in all known leptin receptor isoforms
    Olivia Osborn
    Molecular and Integrative Neurosciences Department, The Harold L Dorris Neurological Research Institute, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell Mol Neurobiol 30:23-33. 2010
    ....
  55. doi Sensors of the innate immune system: their link to rheumatic diseases
    Argyrios N Theofilopoulos
    Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Nat Rev Rheumatol 6:146-56. 2010
    ..These findings have resulted in a critical reappraisal of pathogenetic mechanisms, and provide a basis for the development of novel diagnostic and therapeutic modalities for these diseases...
  56. pmc NK-cell-mediated killing of target cells triggers robust antigen-specific T-cell-mediated and humoral responses
    Philippe Krebs
    Department of Genetics, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Blood 113:6593-602. 2009
    ..We think that the recognition and killing of target cells by NK cells represents an important pathway for the generation of robust CD8+ T and humoral responses that may be exploited for vaccine development...
  57. pmc Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery
    Michael J Barnes
    Department of Genetics, The Scripps Research Institute, La Jolla, CA, USA
    PLoS Biol 7:e51. 2009
    ..Furthermore, we show that peripheral T(reg) cells are a dynamic population that may expand to limit immunopathology or promote chronic infection...
  58. pmc MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands
    Katharina Brandl
    Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 107:19967-72. 2010
    ..A TLR→MyD88→AREG/EREG→EGFR signaling pathway is represented in nonhematopoietic cells of the intestinal tract, responds to microbial stimuli once barriers are breached, and mediates protection against DSS-induced colitis...
  59. ncbi Sensitizing anthrax lethal toxin-resistant macrophages to lethal toxin-induced killing by tumor necrosis factor-alpha
    Sung O Kim
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:7413-21. 2003
    ..Our data indicate that host responses to anthrax infection contribute to cytolysis of LeTx- resistant macrophages...
  60. pmc Flt3 permits survival during infection by rendering dendritic cells competent to activate NK cells
    Celine Eidenschenk
    Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 107:9759-64. 2010
    ..In the absence of Flt3 signaling, NK cell activation is delayed and survival during MCMV infection is markedly compromised...
  61. ncbi Type I interferons (alpha/beta) in immunity and autoimmunity
    Argyrios N Theofilopoulos
    Immunology Department, The Scripps Research Institute, La Jolla, California 92037, USA
    Annu Rev Immunol 23:307-36. 2005
    ....
  62. ncbi TRAF3: a new component of the TLR-signaling apparatus
    Kasper Hoebe
    Department of Immunology, IMM 31, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Trends Mol Med 12:187-9. 2006
    ..Recently, two studies have shown that tumor-necrosis factor receptor-associated factor 3 (TRAF3) is an essential component of the TLR-signaling pathway, being a crucial regulator in the induction of TLR-specific inflammatory responses...
  63. ncbi TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity
    Roberto Baccala
    The Scripps Research Institute, Department of Immunology, La Jolla, California 93037, USA
    Nat Med 13:543-51. 2007
    ....
  64. ncbi Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression
    Motoyuki Otsuka
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Immunity 27:123-34. 2007
    ..Our data suggest that host miRNA can play a role in host interactions with viruses...
  65. ncbi Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria
    Yuki Kinjo
    Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA
    Nat Immunol 7:978-86. 2006
    ....
  66. ncbi LPS, dsRNA and the interferon bridge to adaptive immune responses: Trif, Tram, and other TIR adaptor proteins
    Kasper Hoebe
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Endotoxin Res 10:130-6. 2004
    ..Here, we discuss how Trif and type I IFN are involved in the optimization of APC-T cell interaction in response not only to viral but also bacterial stimuli...
  67. pmc Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice
    Xin Du
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    Genetics 166:331-40. 2004
    ..Velvet is the first known dominant representative of the Egfr allelic series that is fully viable, a fact that makes it particularly useful for developmental studies...
  68. ncbi The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9
    Koichi Tabeta
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Immunol 7:156-64. 2006
    ..Innate responses to nucleic acids and exogenous antigen presentation, which both initiate in endosomes, thus seem to depend on an endoplasmic reticulum-resident protein, which suggests communication between these organellar systems...
  69. pmc Hypomorphic mutation in the site-1 protease Mbtps1 endows resistance to persistent viral infection in a cell-specific manner
    Daniel L Popkin
    Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Host Microbe 9:212-22. 2011
    ..These results support in vivo targeting of Mbtps1 in the treatment of arenavirus infections and demonstrate a critical role for dendritic cells in persistent viral infections...
  70. pmc Mice with mutations of Dock7 have generalized hypopigmentation and white-spotting but show normal neurological function
    Amanda L Blasius
    Departments of Genetics and Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:2706-11. 2009
    ..However, DOCK7 has non-redundant role(s) related to the distribution and function of dermal and follicular melanocytes...
  71. pmc Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility
    Irina Smirnova
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 100:6075-80. 2003
    ..Collectively, however, rare TLR4 coding variants were markedly over-represented. Sensing via TLR4 probably contributes to the early containment of meningococcal infection, and sensing defects create increased risk of disease...
  72. ncbi Not "molecular patterns" but molecules
    Bruce Beutler
    Department of Immunology, IMM 31, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Immunity 19:155-6. 2003
  73. pmc A catechol-O-methyltransferase that is essential for auditory function in mice and humans
    Xin Du
    Department of Genetics, Institute for Childhood and Neglected Diseases, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 105:14609-14. 2008
    ..Our studies identify a previously undescribed COMT gene and indicate an unexpected role for catecholamines in the function of auditory and vestibular sense organs...
  74. ncbi SHIP, TGF-beta, and endotoxin tolerance
    Bruce Beutler
    Department of Immunology, IMM31, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Immunity 21:134-5. 2004
    ....
  75. pmc The serine protease TMPRSS6 is required to sense iron deficiency
    Xin Du
    Department of Genetics, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 320:1088-92. 2008
    ..TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption...
  76. pmc A toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria
    Philippe Georgel
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Infect Immun 73:4512-21. 2005
    ..These observations reveal the existence of a regulated, lipid-based antimicrobial effector pathway in mammals and suggest new approaches to the treatment or prevention of infections with gram-positive bacteria...

Research Grants20

  1. Mutagenetic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2007
    ..This work will enrich our understanding of how and why infections are sometimes lethal. ..
  2. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2005
    ..Fourth, circumvention of the toleragenic mechanism might be used to prevent normal gestation, leading to termination of pregnancy within a few days following implantation of the blastocyst. ..
  3. TLR4 AS AN LPS SENSOR AND SUSCEPTIBILITY LOCUS
    Bruce Beutler; Fiscal Year: 2003
    ..Lps/n, the common wild-type Lps allele; Tlr4/Lps-d, the Lps/d allele of Tlr4; Tlr4/Lps-n, the Lps/n allele of Tlr4. ..
  4. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2003
    ..In the case of mutations that abolish LPS tolerance, we will attempt to determine the net impact on host resistance to infection. ..
  5. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2003
    ..Fourth, circumvention of the toleragenic mechanism might be used to prevent normal gestation, leading to termination of pregnancy within a few days following implantation of the blastocyst. ..
  6. TLR4 AS AN LPS SENSOR AND SUSCEPTIBILITY LOCUS
    Bruce Beutler; Fiscal Year: 2001
    ..Lps/n, the common wild-type Lps allele; Tlr4/Lps-d, the Lps/d allele of Tlr4; Tlr4/Lps-n, the Lps/n allele of Tlr4. ..
  7. TLR4 AS AN LPS SENSOR AND SUSCEPTIBILITY LOCUS
    Bruce Beutler; Fiscal Year: 2002
    ..Lps/n, the common wild-type Lps allele; Tlr4/Lps-d, the Lps/d allele of Tlr4; Tlr4/Lps-n, the Lps/n allele of Tlr4. ..
  8. TLR4 as an LPS sendor and susceptibility locus
    Bruce Beutler; Fiscal Year: 2007
    ..The new mutations that are found--and those that have already been found in preliminary efforts--will be isolated by positional cloning. ..
  9. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2006
    ..In the case of mutations that abolish LPS tolerance, we will attempt to determine the net impact on host resistance to infection. ..
  10. Forward Genetic Analysis of the Innate Immune Contribution to MCMV Resistance
    Bruce Beutler; Fiscal Year: 2006
    ..Because it is clear that innate immunity is degenerate in that individual proteins frequently offer broad defense against bacterial, viral, and fungal pathogens, these studies will yield insight into innate immune mechanisms at large. ..
  11. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2006
    ..Fourth, circumvention of the toleragenic mechanism might be used to prevent normal gestation, leading to termination of pregnancy within a few days following implantation of the blastocyst. ..
  12. TLR4 as an LPS sendor and susceptibility locus
    Bruce Beutler; Fiscal Year: 2006
    ..The new mutations that are found--and those that have already been found in preliminary efforts--will be isolated by positional cloning. ..
  13. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2005
    ..In the case of mutations that abolish LPS tolerance, we will attempt to determine the net impact on host resistance to infection. ..
  14. TLR4 as an LPS sendor and susceptibility locus
    Bruce Beutler; Fiscal Year: 2005
    ..The new mutations that are found--and those that have already been found in preliminary efforts--will be isolated by positional cloning. ..
  15. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2004
    ..In the case of mutations that abolish LPS tolerance, we will attempt to determine the net impact on host resistance to infection. ..
  16. TLR4 as an LPS sendor and susceptibility locus
    Bruce Beutler; Fiscal Year: 2004
    ..The new mutations that are found--and those that have already been found in preliminary efforts--will be isolated by positional cloning. ..
  17. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2004
    ..Fourth, circumvention of the toleragenic mechanism might be used to prevent normal gestation, leading to termination of pregnancy within a few days following implantation of the blastocyst. ..
  18. TLR4 AS AN LPS SENSOR AND SUSCEPTIBILITY LOCUS
    Bruce Beutler; Fiscal Year: 2000
    ..Lps/n, the common wild-type Lps allele; Tlr4/Lps-d, the Lps/d allele of Tlr4; Tlr4/Lps-n, the Lps/n allele of Tlr4. ..