Research Topics
Species | Dennis KasperSummaryAffiliation: Harvard University Country: USA Publications
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Publications
A paradigm for commensalism: the role of a specific microbial polysaccharide in health and diseaseDennis L Kasper
Channing Laboratory, Brigham and Women s Hospital and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
Nestle Nutr Workshop Ser Pediatr Program 64:1-8; discussion 8-10, 251-7. 2009..Thus polysaccharides of the bacterial microbiota can mediate the critical balance between health and disease in the host. As evidence accumulates, this concept is being accepted as an important feature of the immune repertoire...
Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3- and complement receptor 2-deficient miceOlga Pozdnyakova
Department of Pathology, Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
J Immunol 170:84-90. 2003..The normal immune response in wild-type mice may require localization of polysaccharide to marginal zone B cells with subsequent transfer of the Ag to follicular dendritic cells...
A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2Qun Wang
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 203:2853-63. 2006..fragilis. Commensal bacteria, using molecules like PSA, potentially modulate the Th1/Th2 cell balance and the response to infection by coordinating both the innate and adaptive pathways...- CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanismDoo Ryeon Chung
Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
J Immunol 170:1958-63. 2003..These data delineate the specific T cell response necessary for the development of intra-abdominal abscesses and underscore the role of IL-17 in this disease process... - Novel tools for modulating immune responses in the host-polysaccharides from the capsule of commensal bacteriaSuryasarathi Dasgupta
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, USA
Adv Immunol 106:61-91. 2010..These molecules can be used to elucidate the basic biology of the mammalian intestine and have the potential for use in novel therapeutic regimens for various systemic or intestinal pathological conditions... - A unique structural pattern shared by T-cell-activating and abscess-regulating zwitterionic polysaccharidesYong-Hoon Choi
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Biochemistry 41:15144-51. 2002..These results support our hypothesis that T-cell-activating ZPSs assume similar conformational and charge patterns that are recognized by specific receptors and that account for their common property as T-cell activators... - Quantitative determination of immunoglobulin G specific for group B streptococcal beta C protein in human maternal serumCatherine S Lachenauer
Channing Laboratory and Division of Infectious Diseases, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
J Infect Dis 185:368-74. 2002..This difference was not explained by a major difference in epitope specificity... - Zwitterionic capsular polysaccharides: the new MHCII-dependent antigensBrian A Cobb
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Cell Microbiol 7:1398-403. 2005..In this review, we explore what is currently known about ZPS processing and presentation within antigen-presenting cells (APCs) and the immune response that follows... - Microbial carbohydrate depolymerization by antigen-presenting cells: deamination prior to presentation by the MHCII pathwayJinyou Duan
Department of Medicine, Channing Laboratory, Brigham and Women s Hospital and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 105:5183-8. 2008..RNSs and ROSs may be involved in the presentation of glycopeptides by MHC molecules via the processing of other carbohydrate-containing antigens, such as bacterial or viral glycoproteins or glycoconjugate vaccines... - IFN-gamma regulated chemokine production determines the outcome of Staphylococcus aureus infectionRachel M McLoughlin
Department of Medicine, Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
J Immunol 181:1323-32. 2008..aureus pathogenesis by facilitating bacterial survival within the neutrophil. These findings suggest avenues for novel immunomodulatory approaches to control S. aureus infections... - An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune systemSarkis K Mazmanian
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Cell 122:107-18. 2005..These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system... - Type I Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHC II-dependent pathway for antigen presentationChristopher D Velez
Department of Medicine, Channing Laboratory, Harvard Medical School, Boston, MA, USA
Immunology 127:73-82. 2009.... - Role of T cells in abscess formationArthur O Tzianabos
Channing Laboratory, Brigham and Women s Hospital, Departments of Medicine, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
Curr Opin Microbiol 5:92-6. 2002..This work describes how zwitterionic polysaccharides on the surface of these organisms interact with the host immune system in general, and with T cells in particular, to coordinate this pathobiologic response... - How bacterial carbohydrates influence the adaptive immune systemFikri Y Avci
Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Annu Rev Immunol 28:107-30. 2010.... - Type III group B streptococcal polysaccharide induces antibodies that cross-react with Streptococcus pneumoniae type 14Hilde Kari Guttormsen
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Infect Immun 70:1724-38. 2002..When present, these vaccine-induced cross-reacting antibodies conferred in vitro antibody-mediated opsonophagocytosis and killing of both GBS III and Pn14, two pathogens that cause invasive disease in young infants... - Biological chemistry of immunomodulation by zwitterionic polysaccharidesArthur Tzianabos
Department of Medicine, Channing Laboratory, 181 Longwood Ave, Brigham and Women s Hospital, Boston, MA 02115, USA
Carbohydr Res 338:2531-8. 2003..This review will describe the biological and structural aspects of ZPSs that convey these activities... - Glycoconjugate vaccines to prevent group B streptococcal infectionsLawrence C Paoletti
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, Massachusetts 02115, USA
Expert Opin Biol Ther 3:975-84. 2003..Results from these preclinical and clinical studies strongly suggest that GBS conjugate vaccines will be effective in preventing diseases caused by GBS... - Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma/delta T cellsJinyou Duan
Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
Cell Host Microbe 7:140-50. 2010..Thus, commensals orchestrate the expansion of phenotypically distinct gammadelta T cells, and innate immunity is a three-way interaction between host, pathogens, and microbiota... - Induction of cross-reactive antibodies by immunization of healthy adults with types Ia and Ib group B streptococcal polysaccharide-tetanus toxoid conjugate vaccinesAnne Karin Brigtsen
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
J Infect Dis 185:1277-84. 2002..These results indicate that GBS Ia and Ib PSs should be included in a multivalent conjugate vaccine to prevent GBS disease... - Zwitterionic polysaccharides stimulate T cells by MHC class II-dependent interactionsWiltrud M Kalka-Moll
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
J Immunol 169:6149-53. 2002..These results indicate that MHC class II molecules expressing HLA-DR on professional APCs are required for ZPS-induced T cell activation. The implication is that binding of ZPS to HLA-DR may be required for T cell activation... - Construction of designer glycoconjugate vaccines with size-specific oligosaccharide antigens and site-controlled couplingJulia Y Wang
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
Vaccine 21:1112-7. 2003..As an example, we synthesized and evaluated an oligosaccharide-based vaccine against type III group B Streptococcus... - Conjugate vaccines against group B Streptococcus types IV and VIILawrence C Paoletti
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
J Infect Dis 186:123-6. 2002..If needed, types IV and VII CPS conjugate vaccines of the design described can be added to the formulation of a multivalent GBS vaccine... - A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microgliaSeija Lehnardt
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Immunol 177:583-92. 2006..We suggest that this process contributes substantially to the serious morbidity associated with neonatal GBS meningitis and may provide a potential therapeutic target... - Rational chemical design of the carbohydrate in a glycoconjugate vaccine enhances IgM-to-IgG switchingHilde Kari Guttormsen
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, and Institute for Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 105:5903-8. 2008..Targeted chemical engineering of a carbohydrate to create a molecule less like host self may be a rational approach for improving other glycoconjugates... - Orientations of the Bacteroides fragilis capsular polysaccharide biosynthesis locus promoters during symbiosis and infectionErin B Troy
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
J Bacteriol 192:5832-6. 2010..fragilis-induced murine abscesses. Bacteria grown in vivo have greater variability in orientation of polysaccharide locus promoters than culture-grown organisms... - Beneficial effects of Bacteroides fragilis polysaccharides on the immune systemErin B Troy
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Front Biosci 15:25-34. 2010..This review provides an overview of the immunologic properties of PSA including the mechanisms of immune system activation and the resulting immunomodulatory effects... - Polysaccharide processing and presentation by the MHCII pathwayBrian A Cobb
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
Cell 117:677-87. 2004..Our observations begin to elucidate the mechanisms by which some carbohydrates induce important immunologic responses through T cell activation, suggesting a fundamental shift in the MHCII presentation paradigm... - Symbiotic commensal bacteria direct maturation of the host immune systemSanna M Edelman
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
Curr Opin Gastroenterol 24:720-4. 2008..The present review summarizes recent findings in the field and describes new knowledge on the interplay of the innate and adaptive arms of the immune response induced by symbiotic bacterial carbohydrate antigens... - A defined O-antigen polysaccharide mutant of Francisella tularensis live vaccine strain has attenuated virulence while retaining its protective capacityShite Sebastian
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
Infect Immun 75:2591-602. 2007..tularensis type B. Recognition and characterization of the pivotal role of O-PS in the virulence of this intracellular bacterial pathogen may have broad implications for the creation of a safe and efficacious vaccine... - CD4+ T cells regulate surgical and postinfectious adhesion formationDoo Ryeon Chung
Channing Laboratory, Department of Medicine, 181 Longwood Avenue, Boston, MA 02115, USA
J Exp Med 195:1471-8. 2002.... - Deficiency of mannose-binding lectin greatly increases antibody response in a mouse model of vaccinationHilde Kari Guttormsen
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
Clin Immunol 130:264-71. 2009..B1 cells were expanded in peritonium but not in spleen of MBL null mice. The mechanisms of heightened IgG response in MBL null mice were related to C3, and share the same pathway with IgM... - Cellular and humoral immunity are synergistic in protection against types A and B Francisella tularensisShite Sebastian
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
Vaccine 27:597-605. 2009..tularensis and provide important insight into the development of a safer vaccine effective against infections caused by clinical type A and B strains of F. tularensis... - 3-Deoxy-D-manno-octulosonic acid (Kdo) hydrolase identified in Francisella tularensis, Helicobacter pylori, and Legionella pneumophilaSabina Chalabaev
Department of Microbiology and Molecular Genetics, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 285:34330-6. 2010..The identification of this previously faceless enzyme will accelerate study of the biosynthetic basis and biologic impact for postbiosynthetic LPS structural modification... - Bacterial glycans: key mediators of diverse host immune responsesLaurie E Comstock
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Cell 126:847-50. 2006..Here, we discuss the diverse interactions between bacterial glycans and the host immune system... - Modulation of surgical fibrosis by microbial zwitterionic polysaccharidesBegonia Ruiz-Perez
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 102:16753-8. 2005.... - Regulation of virulence by a two-component system in group B streptococcusSheng-Mei Jiang
Channing Laboratory, Brigham and Women's Hospital, Children's Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
J Bacteriol 187:1105-13. 2005..Together, these results indicate that CsrRS regulates expression of multiple GBS virulence determinants and is likely to play an important role in GBS pathogenesis... - Anchors away: contribution of a glycolipid anchor to bacterial invasion of host cellsMiriam J Baron
The Channing Laboratory and the Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
J Clin Invest 115:2325-7. 2005..The mechanism involved most likely relates to the gene product's role in synthesis of a glycolipid anchor for a bacterial cell-surface entity that interacts directly with host cells... - Case records of the Massachusetts General Hospital. Case 25-2005. A 40-year-old man with prolonged fever and weight lossDennis L Kasper
Department of Medicine, Brigham and Women's Hospital, Boston, USA
N Engl J Med 353:713-22. 2005 - Small molecule control of virulence gene expression in Francisella tularensisJames C Charity
Division of Infectious Diseases, Children s Hospital, Harvard Medical School, Boston, Massachusetts, USA
PLoS Pathog 5:e1000641. 2009..Through its responsiveness to ppGpp, the contact between PigR and the MglA-SspA complex allows the integration of nutritional cues into the regulatory network governing virulence gene expression... - Coming of age: carbohydrates and immunityBrian A Cobb
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
Eur J Immunol 35:352-6. 2005..With the common presence of carbohydrate molecules on eukaryotic, prokaryotic, and viral surfaces, the impact of carbohydrates on adaptive immunity is now indisputable... - Zwitterionic polysaccharides stimulate T cells with no preferential V beta usage and promote anergy, resulting in protection against experimental abscess formationFrancesca Stingele
Nestle Research Center, Vers chez les Blanc, Lausanne, Switzerland
J Immunol 172:1483-90. 2004..Taken together, the data show that this class of polysaccharides interacts directly with T cells in a nonbiased manner to elicit an IL-2-dependent anergic response that confers protection against abscess formation... - Safety and immunogenicity of a bivalent group B streptococcal conjugate vaccine for serotypes II and IIICarol J Baker
Sections of Infectious Diseases, Department of Pediatrics, and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
J Infect Dis 188:66-73. 2003..These results support the feasibility of a multivalent vaccine for the 5 prevalent invasive disease-causing GBS CPS serotypes... - Immune response of healthy women to 2 different group B streptococcal type V capsular polysaccharide-protein conjugate vaccinesCarol J Baker
Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
J Infect Dis 189:1103-12. 2004..Infections caused by group B streptococcal (GBS) type V are increasingly common. Capsular polysaccharide (CPS)-protein conjugate GBS vaccines are immunogenic in healthy adults, but type V vaccines have not previously been tested... - Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiaeHerve Tettelin
The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA
Proc Natl Acad Sci U S A 99:12391-6. 2002..agalactiae strains from several serotypes using whole-genome microarrays, revealed the genetic heterogeneity among S. agalactiae strains, even of the same serotype, and provided insights into the evolution of virulence mechanisms... - Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathwaysPhilipp Henneke
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
J Immunol 169:3970-7. 2002..We conclude that the inflammatory, bactericidal, and phagocytic responses to GBS occur via parallel but independent processes... - Effect of B7-2 and CD40 signals from activated antigen-presenting cells on the ability of zwitterionic polysaccharides to induce T-Cell stimulationTom Li Stephen
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Medical Center, Goldenfelsstr. 19-21, 50935 Cologne, Germany
Infect Immun 73:2184-9. 2005..The implication is that activation of ZPS-specific T cells requires an orchestrated arrangement of both presenting and costimulatory molecules to form an immunological synapse... - Role of lipoteichoic acid in the phagocyte response to group B streptococcusPhilipp Henneke
Zentrum für Kinderheilkunde und Jugendmedizin, Albert Ludwigs Universitat Freiburg, Freiburg, Germany
J Immunol 174:6449-55. 2005..In conclusion, LTA from GBS is a TLR2/TLR6 ligand that might contribute to secreted GBS activity, but does not contribute significantly to GBS cell wall mediated macrophage activation... - Identification of a universal Group B streptococcus vaccine by multiple genome screenDomenico Maione
Chiron Srl, Via Fiorentina 1, 53100 Siena, Italy
Science 309:148-50. 2005..Multigenome analysis and screening described here represent a powerful strategy for identifying potential vaccine candidates against highly variable pathogens... - A microbial symbiosis factor prevents intestinal inflammatory diseaseSarkis K Mazmanian
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
Nature 453:620-5. 2008..Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles... - Regulation of surface architecture by symbiotic bacteria mediates host colonizationCui Hua Liu
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 105:3951-6. 2008..These findings suggest a model whereby display of multiple capsular polysaccharides provides essential functions for bacterial colonization during host-symbiont mutualism... - Group A streptococcus epidemiology and vaccine implicationsRonit Cohen-Poradosu
Clin Infect Dis 45:863-5. 2007 - The love-hate relationship between bacterial polysaccharides and the host immune systemSarkis K Mazmanian
Division of Biology, California Institute of Technology, Mail Code 156-29, 1200 East California Boulevard, Pasadena, California 91125, USA
Nat Rev Immunol 6:849-58. 2006..This process seems to contribute to the overall health of the host by offering protection against various diseases and might provide supporting evidence at a molecular level for the 'hygiene hypothesis' of allergic immune disorders... - Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome"Herve Tettelin
Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA
Proc Natl Acad Sci U S A 102:13950-5. 2005..Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes...
Research Grants
- PATHOGENIC MECHANISMS OF ANAEROBES IN SEPSISDennis Kasper; Fiscal Year: 2007..abstract_text> ..
- INFECTIOUS DISEASE AND BASIC MICROBIOLOGICAL MECHANISMSDennis Kasper; Fiscal Year: 2007..Although only eight positions per year are supported by this grant, 175 postdoctoral trainees are currently being funded by our training program in the laboratories of the 39 participating research mentors. ..
- New England Regional Center of Excellence for BiodefenseDennis Kasper; Fiscal Year: 2007..Thus, the NERCE will greatly improve the preparedness of the United States to resist and respond to attacks by infectious agents, whether their source is bioterrorism or nature. ..
- PATHOGENIC MECHANISMS OF ANAEROBES IN SEPSISDennis Kasper; Fiscal Year: 2006..abstract_text> ..
- PATHOGENIC MECHANISMS OF ANAEROBES IN SEPSISDennis Kasper; Fiscal Year: 2001..One of the ultimate goals of this investigation is to understand how polysaccharides activate T cells, which might in turn lead to the design of the interventional strategies for potential new vaccines. ..