Tirap

Summary

Gene Symbol: Tirap
Description: toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
Alias: AA407980, C130027E04Rik, Mal, Tlr4ap, Wyatt, toll/interleukin-1 receptor domain-containing adapter protein, TIR domain-containing adapter protein, Toll-like receptor 4 adaptor protein, adaptor protein Wyatt, myD88 adapter-like protein
Species: mouse

Top Publications

  1. pmc Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
    Edward A Miao
    Institute for Systems Biology, Seattle, Washington, USA
    Nat Immunol 11:1136-42. 2010
  2. doi Long-term exposure to IL-1beta enhances Toll-IL-1 receptor-mediated inflammatory signaling in murine airway hyperresponsiveness
    Yaping Zhang
    Division of ENT Diseases, Department of CLINTEC, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden
    Eur Cytokine Netw 20:148-56. 2009
  3. pmc MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals
    Chun Jen Chen
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 116:2262-71. 2006
  4. pmc Endotoxin uptake in mouse liver is blocked by endotoxin pretreatment through a suppressor of cytokine signaling-1-dependent mechanism
    Melanie J Scott
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Hepatology 49:1695-708. 2009
  5. ncbi Essential roles for NF-kappa B and a Toll/IL-1 receptor domain-specific signal(s) in the induction of I kappa B-zeta
    Akiko Eto
    Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812 8582, Japan
    Biochem Biophys Res Commun 301:495-501. 2003
  6. ncbi Toll-IL-1 receptor domain-containing adaptor protein is critical for early lung immune responses against Escherichia coli lipopolysaccharide and viable Escherichia coli
    Samithamby Jeyaseelan
    Division of Respiratory Infections, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Immunol 175:7484-95. 2005
  7. pmc NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1
    Sinead M Miggin
    School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
    Proc Natl Acad Sci U S A 104:3372-7. 2007
  8. ncbi IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection
    Cecile M Fremond
    University of Orleans, Centre National de la Recherche Scientifique, Molecular Immunology and Embryology, Orleans, France
    J Immunol 179:1178-89. 2007
  9. pmc TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta
    Jonathan C Kagan
    Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Immunol 9:361-8. 2008
  10. ncbi Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction
    K A Fitzgerald
    Department of Biochemistry, Trinity College, Dublin 2, Ireland
    Nature 413:78-83. 2001

Research Grants

Scientific Experts

  • Samithamby Jeyaseelan
  • Adarsh Gandhi
  • AIAHO DING
  • Luke A O'Neill
  • AMY HISE
  • KISHORE ALUGUPALLI
  • Romi Ghose
  • Shenghua Zhou
  • Jonathan C Kagan
  • Yaping Zhang
  • Edward A Miao
  • Shizuo Akira
  • Masahiro Yamamoto
  • Dieudonnée Togbe
  • Katherine A Fitzgerald
  • Douglas T Golenbock
  • Bernhard Ryffel
  • Bruce Beutler
  • N J Bernard
  • Ashley Mansell
  • Carmelo Biondo
  • Emilie Doz
  • Valerie F J Quesniaux
  • Philippe Georgel
  • Kasper Hoebe
  • Kamalpreet Nagpal
  • Suzanne Talbot
  • Jian Wen Dong
  • Stefanie N Vogel
  • Paul J Hertzog
  • Clare E Bryant
  • Sinead M Miggin
  • Christopher P Bechtel
  • Nastaran Mohammadi
  • Stephanie Rose
  • Virginie Vasseur
  • Wenji Piao
  • Bruno Schnyder
  • Zhengfan Jiang
  • C L Kennedy
  • Mariana C Ferrero
  • S C Corr
  • Giuseppe Teti
  • Angelina Midiri
  • Concetta Beninati
  • Roberta Galbo
  • Giuseppe Mancuso
  • Yoon Jeong Choi
  • Tu Thi Ngoc Nguyen
  • Anna M Lundberg
  • Kari Ann Shirey
  • Ty Dale Troutman
  • Antonio Layoun
  • G Thomas Brown
  • Hendrik J Nel
  • Timothy E Sweeney
  • Zhuowei Li
  • Claire J Greenhill
  • John W Hollingsworth
  • Jakub Siednienko
  • Annett Halle
  • Sixto M Leal
  • Edward A Medina
  • Kathleen A Smoak
  • Yan Sun
  • Evelyn Dixit
  • Fabio Martinon
  • Leah E Cole
  • Tatyana Lysakova-Devine
  • Eric Pearlman
  • Peter Ulrichts
  • Zhong bin Deng
  • Elaine F Kenny
  • Melanie J Scott
  • Brett Verstak
  • Franz G Bauernfeind
  • Sandra Santos-Sierra
  • George Hajishengallis
  • Douglas L Mann
  • Jesus G Vallejo
  • Duncan J Maskell
  • Sabine Tötemeyer
  • Toshihiko Kobayashi
  • Bo Wei
  • Noha Semaan
  • Rasheed Ahmad
  • E M Palsson-McDermott
  • Brian G Monks
  • Cecile M Fremond
  • Aisling Dunne

Detail Information

Publications85

  1. pmc Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
    Edward A Miao
    Institute for Systems Biology, Seattle, Washington, USA
    Nat Immunol 11:1136-42. 2010
    ..This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system...
  2. doi Long-term exposure to IL-1beta enhances Toll-IL-1 receptor-mediated inflammatory signaling in murine airway hyperresponsiveness
    Yaping Zhang
    Division of ENT Diseases, Department of CLINTEC, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden
    Eur Cytokine Netw 20:148-56. 2009
    ..Understanding cytokine-induced activation of the Toll-IL-1 receptor-mediated inflammatory signaling mechanisms may provide new options for the treatment of airway inflammation and AHR...
  3. pmc MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals
    Chun Jen Chen
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 116:2262-71. 2006
    ..In contrast, other TIR adaptor molecules, TIRAP/Mal, TRIF, and TRAM, are not required for this process...
  4. pmc Endotoxin uptake in mouse liver is blocked by endotoxin pretreatment through a suppressor of cytokine signaling-1-dependent mechanism
    Melanie J Scott
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Hepatology 49:1695-708. 2009
    ..SOCS1 is known to interact with Toll/IL-1 receptor associated protein (TIRAP) and cause TIRAP ubiquitination and degradation, which regulates TLR signaling...
  5. ncbi Essential roles for NF-kappa B and a Toll/IL-1 receptor domain-specific signal(s) in the induction of I kappa B-zeta
    Akiko Eto
    Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812 8582, Japan
    Biochem Biophys Res Commun 301:495-501. 2003
    ..These results indicate the existence of another signal essential for I kappa B-zeta induction, which is specifically mediated by the TIR domain-mediated signaling pathway...
  6. ncbi Toll-IL-1 receptor domain-containing adaptor protein is critical for early lung immune responses against Escherichia coli lipopolysaccharide and viable Escherichia coli
    Samithamby Jeyaseelan
    Division of Respiratory Infections, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Immunol 175:7484-95. 2005
    ..Toll-IL-1R domain-containing adaptor protein (TIRAP) is a key molecule in the TLR4 and 2 signaling...
  7. pmc NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1
    Sinead M Miggin
    School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
    Proc Natl Acad Sci U S A 104:3372-7. 2007
    ..Both use the adapter proteins MyD88 and MyD88 adapter-like (Mal) to activate signaling pathways...
  8. ncbi IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection
    Cecile M Fremond
    University of Orleans, Centre National de la Recherche Scientifique, Molecular Immunology and Embryology, Orleans, France
    J Immunol 179:1178-89. 2007
    ..Mice deficient for IL-1R1, IL-18R, or Toll-IL-1R domain-containing adaptor protein (TIRAP) were compared with MyD88-deficient mice in an acute model of aerogenic MTB infection...
  9. pmc TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta
    Jonathan C Kagan
    Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Immunol 9:361-8. 2008
    Toll-like receptor 4 (TLR4) induces two distinct signaling pathways controlled by the TIRAP-MyD88 and TRAM-TRIF pairs of adaptor proteins, which elicit the production of proinflammatory cytokines and type I interferons, respectively...
  10. ncbi Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction
    K A Fitzgerald
    Department of Biochemistry, Trinity College, Dublin 2, Ireland
    Nature 413:78-83. 2001
    ..Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TIR-domain-containing protein in the human genome...
  11. ncbi TIRAP: an adapter molecule in the Toll signaling pathway
    T Horng
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Nat Immunol 2:835-41. 2001
    ..We have identified and characterized a Toll-interleukin 1 receptor (TIR) domain-containing adapter protein (TIRAP) and have shown that it controls activation of MyD88-independent signaling pathways downstream of TLR4...
  12. pmc LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF
    Katherine A Fitzgerald
    Division of Infectious Disease and Immunology, Department of Medicine, The University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Exp Med 198:1043-55. 2003
    ..TRAM interacts with TRIF, MyD88 adaptor-like protein (Mal)/TIRAP, and TLR4 but not with TLR3...
  13. ncbi Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nature 420:324-9. 2002
    ..Another adaptor, TIRAP (also known as Mal), has been cloned as a molecule that specifically associates with TLR4 and thus may be ..
  14. ncbi The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors
    Tiffany Horng
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 420:329-33. 2002
    ..b>TIRAP, an adaptor protein in the TLR signalling pathway, has been identified and shown to function downstream of TLR4 (..
  15. pmc Neutrophils Directly Recognize Group B Streptococci and Contribute to Interleukin-1β Production during Infection
    Nastaran Mohammadi
    Department of Clinical and Experimental Medicine, University of Messina, 98125, Messina, Italy
    PLoS ONE 11:e0160249. 2016
    ..These cells directly recognize GBS by means of endosomal TLRs and cytosolic sensors, leading to activation of the caspase-1 inflammasome. ..
  16. doi A critical role for the TLR signaling adapter Mal in alveolar macrophage-mediated protection against Bordetella pertussis
    N J Bernard
    School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
    Mucosal Immunol 8:982-92. 2015
    ..Here we examined the role of Toll-like receptor (TLR) adapter protein Mal in the control of B. pertussis infection in the lungs. We found that B...
  17. ncbi Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways
    Noha Semaan
    Laboratoire Physiopathologie des Arthrites, Universite Louis Pasteur de Strasbourg, Unité de Formation et de Recherche Sciences Pharmaceutiques, Illkirch, France
    J Immunol 180:3485-91. 2008
    ..Etk is associated with MyD88, FAK, and Mal as shown by coimmunoprecipitation...
  18. doi Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice
    Toshihiko Kobayashi
    Division of Infectious Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Int Immunol 20:881-91. 2008
    ..Our results suggest that RP105-dependent tonic B cell activation has a pathogenic role in MRL/lpr mice...
  19. doi Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1
    Rasheed Ahmad
    Laboratory of Immunovirology and Viral and Immune Diseases Program, Ste Justine Hospital Research Center and Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, QC, Canada
    Blood 112:2360-8. 2008
    ..Interestingly, TIRAP/Mal, an adaptor molecule specifically recruited to TLR2 and TLR4, was also required for maximal up-regulation of ..
  20. doi Particle-Induced Osteolysis Is Mediated by TIRAP/Mal in Vitro and in Vivo: Dependence on Adherent Pathogen-Associated Molecular Patterns
    Christopher P Bechtel
    Departments of Orthopaedics C P B, J J G, J M T, and E M G and Pathology E M G, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio
    J Bone Joint Surg Am 98:285-94. 2016
    ..for TLR-2 and TLR-4 known as toll/interleukin-1 receptor domain-containing adapter protein/MyD88 adapter-like (TIRAP/Mal)...
  21. doi MAPPIT (mammalian protein-protein interaction trap) analysis of early steps in toll-like receptor signalling
    Peter Ulrichts
    Department of Medical Protein Research, Ghent University VIB, Ghent, Belgium
    Methods Mol Biol 517:133-44. 2009
    ..In the subsequent protocol, we describe the use of MAPPIT to study early events in Toll-like receptor (TLR) signalling. We here demonstrate a "signalling interaction cascade" from TLR4 to IRAK-1...
  22. pmc A Decoy Peptide that Disrupts TIRAP Recruitment to TLRs Is Protective in a Murine Model of Influenza
    Wenji Piao
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Cell Rep 11:1941-52. 2015
    ..Cell imaging, co-immunoprecipitation, and in vitro studies demonstrated that 2R9 preferentially targets TIRAP. 2R9 diminished systemic cytokine responses elicited in vivo by synthetic TLR2 and TLR7 agonists; it inhibited the ..
  23. pmc Distinct roles for Dectin-1 and TLR4 in the pathogenesis of Aspergillus fumigatus keratitis
    Sixto M Leal
    Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America
    PLoS Pathog 6:e1000976. 2010
    ..We also found that TRIF(-/-) and TIRAP(-/-) mice exhibited no fungal-killing defects, but that MyD88(-/-) and IL-1R1(-/-) mice were unable to regulate ..
  24. pmc Lipopolysaccharide signaling without a nucleus: kinase cascades stimulate platelet shedding of proinflammatory IL-1β-rich microparticles
    G Thomas Brown
    Medical Scientist Training Program, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    J Immunol 186:5489-96. 2011
    ..cell-penetrating chimeric peptide inhibitors, and gene-targeted animals to show splicing required MyD88 and TIRAP, and IRAK1/4, Akt, and JNK phosphorylation and activation...
  25. doi Recognition of yeast nucleic acids triggers a host-protective type I interferon response
    Carmelo Biondo
    The Elie Metchnikoff Department, University of Messina, Messina, Italy
    Eur J Immunol 41:1969-79. 2011
    ..These data suggest that recognition of yeast nucleic acids by TLR7 and TLR9 triggers a host-protective IFN-α/β response...
  26. doi Toll-like receptor 3 and 4 signalling through the TRIF and TRAM adaptors in haematopoietic cells promotes atherosclerosis
    Anna M Lundberg
    Center for Molecular Medicine, Department of Medicine at Karolinska University Hospital Solna, Karolinska Institutet, Stockholm SE 17176, Sweden
    Cardiovasc Res 99:364-73. 2013
    ..of TLRs in immune cells are pro-atherogenic, we analysed the role of the TLR-specific adaptors MyD88 adaptor-like (MAL), TRIF-related adaptor molecule (TRAM), and TIR-domain-containing adaptor-inducing interferon-β (TRIF) in ..
  27. doi MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C
    S C Corr
    Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
    Mucosal Immunol 7:57-67. 2014
    MyD88 adapter-like (Mal)-deficient mice displayed increased susceptibility to oral but not intraperitoneal infection with Salmonella Typhimurium...
  28. doi Differential role of MyD88 and Mal/TIRAP in TLR2-mediated gastric tumourigenesis
    C L Kennedy
    Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia
    Oncogene 33:2540-6. 2014
    ..However, little is known about the in vivo role of MyD88 adapter-like (Mal)/TIR-domain containing adapter protein (TIRAP), which is restricted to facilitating TLR4 and TLR2 signalling...
  29. pmc Key role of Toll-like receptor 2 in the inflammatory response and major histocompatibility complex class ii downregulation in Brucella abortus-infected alveolar macrophages
    Mariana C Ferrero
    Instituto de Estudios de la Inmunidad Humoral CONICET UBA, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina
    Infect Immun 82:626-39. 2014
    ..Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival. ..
  30. ncbi Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4
    Nobutaka Suzuki
    Amgen Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario M5G 2C1, Canada
    Nature 416:750-6. 2002
    ..In addition, animals lacking IRAK-4 are severely impaired in their responses to viral and bacterial challenges. Our results indicate that IRAK-4 has an essential role in innate immunity...
  31. ncbi Toll-like receptor 4 and Toll-IL-1 receptor domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 adapter-like (Mal) contribute to maximal IL-6 expression in macrophages
    Dagmar Schilling
    Pulmonary Center, School of Medicine, Boston University, Boston, MA 02118, USA
    J Immunol 169:5874-80. 2002
    ..expression via a mechanism that requires the adapter protein Toll-IL-1R domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 (MyD88) adapter-like (Mal), but not the adapter protein MyD88...
  32. ncbi Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation
    Ashley Mansell
    Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia
    Nat Immunol 7:148-55. 2006
    ..The adaptor protein Mal is specifically involved in signaling via TLR2 and TLR4...
  33. ncbi Nonredundant roles of TIRAP and MyD88 in airway response to endotoxin, independent of TRIF, IL-1 and IL-18 pathways
    Dieudonnée Togbe
    Molecular Immunology and Embryology, CNRS UMR6218, Transgenose Institute, Orleans, France
    Lab Invest 86:1126-35. 2006
    ..However, the relative roles of the TLR4 adaptor proteins TIRAP and TRIF and of the MyD88-dependent IL-1 and IL-18 receptor pathways in this response are unclear...
  34. pmc Peroxisomes are signaling platforms for antiviral innate immunity
    Evelyn Dixit
    Division of Gastroenterology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Cell 141:668-81. 2010
    ..The interferon regulatory factor IRF1 plays a crucial role in regulating MAVS-dependent signaling from peroxisomes. These results establish that peroxisomes are an important site of antiviral signal transduction...
  35. pmc Phosphatidylinositol 4-phosphate 5-kinase α facilitates Toll-like receptor 4-mediated microglial inflammation through regulation of the Toll/interleukin-1 receptor domain-containing adaptor protein (TIRAP) location
    Tu Thi Ngoc Nguyen
    Chronic Inflammatory Disease Research Center, Neuroscience Graduate Program, Graduate School of Interdisciplinary Programs, Ajou University, Suwon, Gyeonggi 443 721, South Korea
    J Biol Chem 288:5645-59. 2013
    ..is also known to mediate plasma membrane localization of the Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), required for the MyD88-dependent Toll-like receptor (TLR) 4 signaling pathway...
  36. pmc Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice
    Adarsh Gandhi
    University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030, USA
    Toxicol Appl Pharmacol 266:430-8. 2013
    ..of TLRs recruits the first adaptor protein, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) to the TIR domain of TLRs leading to the activation of the downstream kinase, c-Jun-N-terminal kinase (JNK)...
  37. pmc PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment
    Yoon Jeong Choi
    Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA
    FASEB J 27:243-54. 2013
    ..responses, we hypothesized that PTEN regulated TLR5-induced responses by controlling the involvement of Mal in TLR5 engagement...
  38. doi Toll-like receptor signal adaptor protein MyD88 is required for sustained endotoxin-induced acute hypoferremic response in mice
    Antonio Layoun
    Montreal Cancer Institute, University of Montreal, Montreal, Quebec, Canada
    Am J Pathol 180:2340-50. 2012
    ..Together, these results suggest that targeting specific TLR signaling pathways by affecting the function of adaptor molecules may provide new strategies to counteract iron sequestration within macrophages during inflammation...
  39. pmc Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt
    Ty Dale Troutman
    Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 109:273-8. 2012
    ..Our results demonstrate that BCAP is a unique TIR domain-containing TLR signaling adapter crucial for linking TLRs to PI3K activation and regulating the inflammatory response...
  40. pmc Hyaluronan signaling during ozone-induced lung injury requires TLR4, MyD88, and TIRAP
    Zhuowei Li
    Department of Medicine, Duke University, Durham, North Carolina, United States of America
    PLoS ONE 6:e27137. 2011
    ..Using a murine model of AHR, C57BL/6J, TLR4-/-, MyD88-/-, and TIRAP-/- mice were characterized for AHR after exposure to either ozone (1 ppm × 3 h) or HA fragments...
  41. ncbi Mapping, genetic isolation, and characterization of genetic loci that determine resistance to atherosclerosis in C3H mice
    Susanna S Wang
    UCLA School of Medicine, Dept of Human Genetics, Box 95167, University of California at Los Angeles, Los Angeles, CA 90095 1679, USA
    Arterioscler Thromb Vasc Biol 27:2671-6. 2007
    ..To identify the genetic factors involved in lesion initiation, we studied a cross between C3H and the susceptible strain C57BL/6J (B6) on a hyperlipidemic (apolipoprotein E-null) background...
  42. ncbi TLR4 up-regulation at protein or gene level is pathogenic for lupus-like autoimmune disease
    Bei Liu
    Department of Immunology, Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030 1601, USA
    J Immunol 177:6880-8. 2006
    ..Our study has revealed that increased TLR4 signaling alone without exogenous insult can break immunological tolerance. It provides a strong experimental evidence for TLR4 dysregulation as an etiology of lupus-like renal disease...
  43. ncbi Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling
    Jonathan C Kagan
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Cell 125:943-55. 2006
    ..Signaling downstream from TLRs is initiated by the recruitment of adaptor proteins, including MyD88 and TIRAP. These adaptors play essential roles in TLR signaling, but the mechanism of their function is currently unknown...
  44. doi Phosphatidylinositol 3-kinase activation attenuates the TLR2-mediated macrophage proinflammatory cytokine response to Francisella tularensis live vaccine strain
    Edward A Medina
    Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
    J Immunol 185:7562-72. 2010
    ..This TLR2-independent inhibitory pathway may be an important mechanism by which Francisella suppresses the host's innate immune response...
  45. doi IL-6 trans-signaling modulates TLR4-dependent inflammatory responses via STAT3
    Claire J Greenhill
    Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia
    J Immunol 186:1199-208. 2011
    ..Additional genetic approaches demonstrated that the TLR4/Mal pathway contributed to LPS hypersensitivity and increased IL-6 production in gp130(F/F) mice...
  46. pmc Differential role of Toll-interleukin 1 receptor domain-containing adaptor protein in Toll-like receptor 2-mediated regulation of gene expression of hepatic cytokines and drug-metabolizing enzymes
    Romi Ghose
    College of Pharmacy, Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 1441 Moursund St, Houston, TX 77030, USA
    Drug Metab Dispos 39:874-81. 2011
    ..ligand, which initiates signaling by recruitment of Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) to the cytoplasmic TIR domain of TLR2...
  47. doi Impaired basophil induction leads to an age-dependent innate defect in type 2 immunity during helminth infection in mice
    Hendrik J Nel
    Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland
    J Immunol 186:4631-9. 2011
    ..brasiliensis. The defect in juvenile mice with regard to helminth-induced innate basophil-mediated type 2 response is relevant to allergic conditions...
  48. pmc Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity
    Troy Querec
    Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA
    J Exp Med 203:413-24. 2006
    ..Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses...
  49. ncbi Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4, TRIF, or TRAM
    Amy G Hise
    Center for Global Health and Diseases and Department of Ophthalmology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    J Immunol 178:1068-76. 2007
    ..whereas responses were absent in macrophages from MyD88(-/-) and Toll/IL-1R domain-containing adaptor protein (TIRAP)/MyD88 adaptor-like (Mal) deficient mice...
  50. pmc A toll-like receptor 2 pathway regulates the Ppargc1a/b metabolic co-activators in mice with Staphylococcal aureus sepsis
    Timothy E Sweeney
    Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America
    PLoS ONE 6:e25249. 2011
    ..By comparing their responses to S. aureus with WT mice, we found that MyD88-deficient and MAL-deficient mice expressed hepatic Ppargc1a and Ppargc1b normally, but that neither gene was activated in TRAM-..
  51. pmc Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury
    Dieudonnée Togbe
    Molecular Immunology and Embryology, University of Orléans and CNRS UMR6218, Transgenose Institute, Orleans, France
    Int J Exp Pathol 88:387-91. 2007
    ..myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adaptor protein (TIRAP), but independent of TIR-domain-containing adaptor-inducing interferon-beta (TRIF)...
  52. doi TLR3-mediated IFN-β gene induction is negatively regulated by the TLR adaptor MyD88 adaptor-like
    Jakub Siednienko
    Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Maynooth, Co Kildare, Kildare, Ireland
    Eur J Immunol 40:3150-60. 2010
    ..Herein, we sought to perform analysis to definitively assign a mechanistic role for MyD88 adaptor-like (Mal), an activator of TLR2/4 signalling, in the negative regulation of TLR3/TRIF signalling...
  53. ncbi Acylation determines the toll-like receptor (TLR)-dependent positive versus TLR2-, mannose receptor-, and SIGNR1-independent negative regulation of pro-inflammatory cytokines by mycobacterial lipomannan
    Emilie Doz
    Orleans University and CNRS, Molecular Immunology and Embryology, UMR6218, 45071 Orleans, France
    J Biol Chem 282:26014-25. 2007
    ..an agonist of TLR2/TLR1, promoted interleukin-12 p40 and NO secretion through the adaptor proteins MyD88 and TIRAP, whereas the fraction containing tetra-acylated LM activated macrophages in a MyD88-dependent fashion, mostly ..
  54. 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
    ..response pathway in which the adapter TRAM has predominant importance, absent any need for MyD88 or Mal, and with only a partial requirement for TRIF. Downstream of TRAM, IRF7 activation leads to a type I IFN response...
  55. ncbi TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium
    Sarah L Lebeis
    Microbiology and Molecular Genetics Graduate Program, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 165 Michael Street, Atlanta, GA 30322, USA
    J Immunol 179:566-77. 2007
    ..Taken together, these experiments provide evidence for a protective role of innate immune signaling in infections caused by attaching and effacing pathogens...
  56. pmc Salmonella-induced SipB-independent cell death requires Toll-like receptor-4 signalling via the adapter proteins Tram and Trif
    Pamela Cook
    Centre for Veterinary Science, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
    Immunology 122:222-9. 2007
    ..membrane of Gram-negative bacteria and is recognized by Toll-like receptor 4, signalling via the adapter proteins Mal, MyD88, Tram and Trif. Here we show that S...
  57. ncbi The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I
    Simon Rothenfusser
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 175:5260-8. 2005
    ..normally in cells from mice with targeted deletions of the Toll-IL-1 resistance domain containing adapters MyD88, Mal, Toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF), and TRIF-related adaptor molecule TLR3, or the E3 ..
  58. ncbi Expression of many immunologically important genes in Mycobacterium tuberculosis-infected macrophages is independent of both TLR2 and TLR4 but dependent on IFN-alphabeta receptor and STAT1
    Shuangping Shi
    Program in Immunology and Microbial Pathogenesis, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA
    J Immunol 175:3318-28. 2005
    ....
  59. ncbi TIR domain-containing adaptors define the specificity of TLR signaling
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Mol Immunol 40:861-8. 2004
    ..Indeed, two additional TIR domain-containing adaptors, TIRAP/Mal and TRIF, have recently been identified. Both define the specific biological responses of each TLR.
  60. pmc Murine cerebral malaria development is independent of toll-like receptor signaling
    Dieudonnée Togbe
    Molecular Immunology and Embryology, Centre National de la Recherche Scientifique, and University of Orleans, Transgenose Institute, Orleans, France
    Am J Pathol 170:1640-8. 2007
    ..we infected mice deficient for single TLR1, -2, -3, -4, -6, -7, or -9 and their adapter proteins MyD88, TIRAP, and TRIF...
  61. ncbi Toll-like receptor signal transduction and the tailoring of innate immunity: a role for Mal?
    Luke A J O'Neill
    Dept of Biochemistry, Trinity College, Dublin, Ireland
    Trends Immunol 23:296-300. 2002
    ..of different signalling adapters, with MyD88 being used by several TLRs, and the adapter MyD88-adapter-like (Mal) being recruited specifically by TLR-4...
  62. pmc A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis
    Chiea C Khor
    The Wellcome Trust Centre for Human Genetics, University of Oxford, UK
    Nat Genet 39:523-8. 2007
    ..The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6)...
  63. pmc Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance
    Zhong bin Deng
    Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
    Diabetes 58:2498-505. 2009
    ..We sought to determine whether exosome-like vesicles (ELVs) released from adipose tissue play a role in activation of macrophages and subsequent development of insulin resistance in a mouse model...
  64. ncbi The role of hyaluronan degradation products as innate alloimmune agonists
    B M Tesar
    Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven CT, Connecticut, USA
    Am J Transplant 6:2622-35. 2006
    ..In conclusion, our study suggests that fragments of hyaluronan can act as innate immune agonists that activate alloimmunity...
  65. pmc Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88/Mal-dependent inflammatory responses
    Shenghua Zhou
    Department of Medicine, University of Massachusetts Medical Center, 364 Plantation Street, Lazare Research Building, Worcester, MA 01605, USA
    J Neuroimmunol 194:70-82. 2008
    ..central nervous system (CNS) glial cells are activated by Lymphocytic Choriomeningitis Virus (LCMV) in a TLR2-MyD88/Mal-dependent manner...
  66. ncbi Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response
    Sara W Montminy
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nat Immunol 7:1066-73. 2006
    ..required TLR4, the adaptor protein MyD88 and coreceptor MD-2 and was considerably enhanced by CD14 and the adaptor Mal. Both innate and adaptive responses were required for sterilizing immunity against the modified strain, and ..
  67. ncbi Toll-like receptor 2 modulates left ventricular function following ischemia-reperfusion injury
    Yasushi Sakata
    Winters Center for Heart Failure Research, 1709 Dryden BCM, 620 Rm 9 83, Houston, TX 77030, USA
    Am J Physiol Heart Circ Physiol 292:H503-9. 2007
    ..Thus disruption of TLR2-mediated signaling may be helpful to induce immediate or delayed myocardial protection from ischemia-reperfusion injury...
  68. pmc Induction of distinct TLR2-mediated proinflammatory and proadhesive signaling pathways in response to Porphyromonas gingivalis fimbriae
    George Hajishengallis
    Department of Periodontics Oral Health and Systemic Disease, University of Louisville Health Sciences Center, Louisville, KY 40292, USA
    J Immunol 182:6690-6. 2009
    ..pathway is dependent on the adaptor molecules Toll/IL-1 receptor domain-containing adaptor protein (also known as Mal) and MyD88, the proadhesive pathway is Toll/IL-1 receptor domain-containing adaptor protein/MyD88-independent and ..
  69. pmc Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression
    Franz G Bauernfeind
    Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 183:787-91. 2009
    ..Signals provided by NF-kappaB activators are necessary but not sufficient for NLRP3 activation, and a second stimulus such as ATP or crystal-induced damage is required for NLRP3 activation...
  70. pmc Mal connects TLR2 to PI3Kinase activation and phagocyte polarization
    Sandra Santos-Sierra
    Center for Pediatrics and Adolescent Medicine and Centre of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg 79106, Germany
    EMBO J 28:2018-27. 2009
    ..to essentially require both adaptor proteins MyD88 (myeloid differentiation primary response gene 88) and Mal/TIRAP (MyD88-adapter-like/TIR-domain-containing adaptor protein)...
  71. pmc MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses
    Brett Verstak
    Centre for Innate Immunity and Infectious Disease, Monash Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia
    J Biol Chem 284:24192-203. 2009
    ..MyD88 adapter-like (Mal), also termed TIRAP, is involved in bridging MyD88 to the receptor complex for TLR-2 and TLR4 signaling in response to bacterial ..
  72. pmc TLR4 and TLR5 on corneal macrophages regulate Pseudomonas aeruginosa keratitis by signaling through MyD88-dependent and -independent pathways
    Yan Sun
    Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA
    J Immunol 185:4272-83. 2010
    ..IL-1α and IL-1β are also produced, which activate an IL-1R1/MyD88-positive feedback loop in macrophages and IL-1R on other resident cells in the cornea...
  73. 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...
  74. pmc Phagosomal retention of Francisella tularensis results in TIRAP/Mal-independent TLR2 signaling
    Leah E Cole
    Department of Microbiology and Immunology, University of Maryland, Baltimore, Baltimore, MD 21201, USA
    J Leukoc Biol 87:275-81. 2010
    ..The two adaptor proteins associated with TLR2-mediated signaling are MyD88 and TIRAP. Although MyD88 is absolutely required for the Ft-induced macrophage cytokine response, the requirement for TIRAP ..
  75. pmc Toll-like receptor 4 signalling through MyD88 is essential to control Salmonella enterica serovar typhimurium infection, but not for the initiation of bacterial clearance
    Suzanne Talbot
    Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
    Immunology 128:472-83. 2009
    ..TLR4 signals through the adapter proteins Mal/MyD88 and TRIF-related adaptor molecule (TRAM)/TIR-domain-containing adaptor-inducing interferon-b (TRIF)...
  76. pmc Innate immunity mediates myocardial preconditioning through Toll-like receptor 2 and TIRAP-dependent signaling pathways
    Jian Wen Dong
    Department of Medicine, Winters Center for Heart Failure Research, Baylor College of Medicine and Texas Children s Hospital, Houston, USA
    Am J Physiol Heart Circ Physiol 298:H1079-87. 2010
    ..wild-type (WT) mice and mice deficient in TLR2 (TLR2D), TLR4 (TLR4D), and TIR domain-containing adapter protein (TIRAP-D) to ischemic preconditioning (IPC)...
  77. pmc TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages
    Fabio Martinon
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA
    Nat Immunol 11:411-8. 2010
    ..Our findings identify an unsuspected critical function for XBP1 in mammalian host defenses...
  78. ncbi MyD88- and Bruton's tyrosine kinase-mediated signals are essential for T cell-independent pathogen-specific IgM responses
    Kishore R Alugupalli
    Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA
    J Immunol 178:3740-9. 2007
    ..These results suggest that MyD88 specifically promotes T cell-independent BCR signaling and that, in the absence of Btk, this TLR-mediated stimulation is a required component of this signal...
  79. pmc Myeloid differentiation primary response protein 88 couples reverse cholesterol transport to inflammation
    Kathleen A Smoak
    Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Cell Metab 11:493-502. 2010
    ....
  80. ncbi Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of antibacterial defense in the lung against Klebsiella pneumoniae but not Pseudomonas aeruginosa
    Samithamby Jeyaseelan
    Division of Respiratory Infections, Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA
    J Immunol 177:538-47. 2006
    ..TLRs are essential for innate immune defense. TIRAP (Toll/IL-1R domain-containing adaptor protein) is an adaptor in TLR1, TLR2, TLR4, and TLR6 signaling, whereas ..
  81. doi Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein A46, specifically inhibits TLR4 by directly targeting MyD88 adaptor-like and TRIF-related adaptor molecule
    Tatyana Lysakova-Devine
    Immunology Research Centre, School of Biochemistry and Immunology, Trinity College Dublin, Ireland
    J Immunol 185:4261-71. 2010
    ..Indeed, VIPER directly interacted with the TLR4 adaptor proteins MyD88 adaptor-like (Mal) and TRIF-related adaptor molecule (TRAM)...
  82. doi MyD88 adaptor-like is not essential for TLR2 signaling and inhibits signaling by TLR3
    Elaine F Kenny
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
    J Immunol 183:3642-51. 2009
    Although a clear role for the adaptor protein myeloid differentiation factor-88 (MyD88) adaptor-like (Mal, or TIRAP) in TLR4 signaling has been demonstrated, there is limited information on its role in TLR2 signaling...
  83. pmc Induction of macrophage-derived SLPI by Mycobacterium tuberculosis depends on TLR2 but not MyD88
    Aihao Ding
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Immunology 116:381-9. 2005
    ..This induction signifies the presence of a TLR2-dependent but MyD88-independent M. tuberculosis signalling pathway, suggesting involvement of adaptor protein(s) other than MyD88 in M. tuberculosis-mediated induction of SLPI...
  84. 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...
  85. pmc Resident enteric microbiota and CD8+ T cells shape the abundance of marginal zone B cells
    Bo Wei
    Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095 1732, USA
    Eur J Immunol 38:3411-25. 2008
    ..Thus, members of certain enteric microbial communities link with CD8(+) T cells as a previously unappreciated mechanism that shapes innate immunity dependent on innate-like B cells...

Research Grants3

  1. MECHANISMS OF NOVEL ANTI-INFLAMMATORY ACTIONS OF SLPI
    Aihao Ding; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  2. Innate immune responses in lymphatic filariasis
    AMY HISE; Fiscal Year: 2007
    ..abstract_text> ..
  3. B1B lymphocytes generate T cell-independent memory
    KISHORE ALUGUPALLI; Fiscal Year: 2009
    ..Understanding the basis for the longevity of the Tl protective responses conferred by B1b cells will provide novel approaches to generate effective vaccines against pathogens expressing Tl antigens. ..