Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis.

Multiple sclerosis is believed to result from a CD4+ T-cell response against myelin antigens. Peptidoglycan, a major component of the Gram-positive bacterial cell wall, is a functional lipopolysaccharide analogue with potent proinflammatory properties and is conceivably a mediator of sterile inflammation. Here we demonstrate that peptidoglycan is present within antigen-presenting cells in the brain of multiple sclerosis patients. These cells have macrophage and dendritic cell characteristics, and are immunocompetent as evidenced by co-expression of inflammatory cytokines and co-stimulatory molecules. In addition, intrathecal plasma cells specific for peptidoglycan are present in multiple sclerosis brain tissue, and antibodies binding peptidoglycan are present in CSF during active disease. Peptidoglycan may thus contribute to T- and B-cell activity during brain inflammation without a requirement for local bacterial replication.

[1]  G. Opdenakker,et al.  Peptidoglycan from sterile human spleen induces T-cell proliferation and inflammatory mediators in rheumatoid arthritis patients and healthy subjects. , 2001, Rheumatology.

[2]  J. Laman,et al.  Reduced systemic IgG levels against peptidoglycan in rheumatoid arthritis (RA) patients , 2001, Clinical and experimental immunology.

[3]  H. Lassmann The New Pathology of Multiple Sclerosis , 2000 .

[4]  J. Laman,et al.  Pararosaniline Fixation for Detection of Co-stimulatory Molecules, Cytokines, and Specific Antibody , 2000, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[5]  J. Noseworthy Progress in determining the causes and treatment of multiple sclerosis , 1999, Nature.

[6]  M. Rothe,et al.  Peptidoglycan- and Lipoteichoic Acid-induced Cell Activation Is Mediated by Toll-like Receptor 2* , 1999, The Journal of Biological Chemistry.

[7]  J. Laman,et al.  Bacterial peptidoglycan polysaccharides in sterile human spleen induce proinflammatory cytokine production by human blood cells. , 1999, The Journal of infectious diseases.

[8]  E. Moreno,et al.  Lysosomal accumulation and recycling of lipopolysaccharide to the cell surface of murine macrophages, an in vitro and in vivo study. , 1999, Journal of immunology.

[9]  D. Relman The search for unrecognized pathogens. , 1999, Science.

[10]  F C Kafatos,et al.  Phylogenetic perspectives in innate immunity. , 1999, Science.

[11]  C. Vinson,et al.  Bacterial Peptidoglycan Induces CD14-dependent Activation of Transcription Factors CREB/ATF and AP-1* , 1999, The Journal of Biological Chemistry.

[12]  M. Foti,et al.  Coordinated events during bacteria-induced DC maturation. , 1999, Immunology today.

[13]  T. Okai,et al.  Fetal Size as a Determinant of Obstetrical Outcome of Post-Term Pregnancy , 1999, Gynecologic and Obstetric Investigation.

[14]  R. Ulevitch Endotoxin opens the Toll gates to innate immunity , 1999, Nature Medicine.

[15]  R. Ulevitch Endotoxin opens the Tollgates to innate immunity. , 1999, Nature medicine.

[16]  R. Landmann,et al.  LBP or the Presentation of LPS / LBP by Blocking Either the Binding of LPS to ( LBP ) Protect Mice from Lethal Endotoxemia Lipopolysaccharide ( LPS )-Binding Protein Monoclonal Antibodies to Murine , 1999 .

[17]  R. Steinman,et al.  Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. , 1998, Science.

[18]  M. Matyszak Inflammation in the CNS: balance between immunological privilege and immune responses , 1998, Progress in Neurobiology.

[19]  H. Lassmann,et al.  Immunopathology of multiple sclerosis: Report on an international meeting held at the Institute of Neurology of the University of Vienna , 1998, Journal of Neuroimmunology.

[20]  R. Steinman,et al.  Antigen processing for amateurs and professionals. , 1998, Trends in cell biology.

[21]  R. Cortese,et al.  CSF-enriched antibodies do not share specificities among MS patients , 1998, Multiple sclerosis.

[22]  H. Flad,et al.  Components of gut bacteria as immunomodulators. , 1998, International journal of food microbiology.

[23]  P. Marrack,et al.  Cytokine-induced survival of activated T cells in vitro and in vivo. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  H. Pircher,et al.  Viral and Bacterial Infections Interfere with Peripheral Tolerance Induction and Activate CD8+ T Cells to Cause Immunopathology , 1998, The Journal of experimental medicine.

[25]  R. Debets,et al.  Inflammatory properties of peptidoglycan are decreased after degradation by human N-acetylmuramyl-L-alanine amidase. , 1997, European cytokine network.

[26]  P. Calabresi,et al.  Association of human herpes virus 6 (HHV-6) with multiple sclerosis: Increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA , 1997, Nature Medicine.

[27]  W. Schaaper,et al.  Screening of a Small Set of Random Peptides: A New Strategy to Identify Synthetic Peptides that Mimic Epitopes , 1997 .

[28]  P. Toivanen,et al.  Muramic acid in human peripheral blood leucocytes in different age groups , 1997, European journal of clinical investigation.

[29]  J. V. van Dongen,et al.  Expression and intracellular localization of the human N-acetylmuramyl-L-alanine amidase, a bacterial cell wall-degrading enzyme. , 1997, Blood.

[30]  C. Janeway,et al.  A human homologue of the Drosophila Toll protein signals activation of adaptive immunity , 1997, Nature.

[31]  P. Marrack,et al.  Interleukin 4 (IL-4) or IL-7 Prevents the Death of Resting T Cells: Stat6 Is Probably Not Required for the Effect of IL-4 , 1997, The Journal of experimental medicine.

[32]  E. Shevach,et al.  Microbial products induce autoimmune disease by an IL-12-dependent pathway. , 1997, Journal of immunology.

[33]  D D Breimer,et al.  The blood-brain barrier in neuroinflammatory diseases. , 1997, Pharmacological reviews.

[34]  H. Flad,et al.  Specific binding of soluble peptidoglycan and muramyldipeptide to CD14 on human monocytes , 1997, Infection and immunity.

[35]  M. Melief,et al.  Purification and characterization of N-acetylmuramyl-L-alanine amidase from human plasma using monoclonal antibodies. , 1996, Biochimica et biophysica acta.

[36]  J. Verhoef,et al.  Intracellular pathways involved in tumor necrosis factor-alpha release by human monocytes on stimulation with lipopolysaccharide or staphylococcal peptidoglycan are partly similar. , 1996, The Journal of infectious diseases.

[37]  M. Melief,et al.  Presence of bacterial flora-derived antigen in synovial tissue macrophages and dendritic cells. , 1995, British journal of rheumatology.

[38]  Hans Lassmann,et al.  Monocyte/macrophage differentiation in early multiple sclerosis lesions , 1995, Annals of neurology.

[39]  P. Oksman,et al.  Muramic acid in peripheral blood leukocytes of healthy human subjects. , 1995, The Journal of infectious diseases.

[40]  P. Linsley,et al.  Lipopolysaccharide interferes with the induction of peripheral T cell death. , 1995, Immunity.

[41]  R. Ravid,et al.  Controls are what makes a brain bank go round , 1995 .

[42]  M. Hazenberg Intestinal flora bacteria and arthritis: why the joint? , 1995, Scandinavian journal of rheumatology. Supplement.

[43]  W. B. van den Berg,et al.  Detection of intestinal flora-derived bacterial antigen complexes in splenic macrophages of rats. , 1994, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[44]  H. Flad,et al.  Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14 monoclonal antibodies and by lipid A partial structures , 1994, Infection and immunity.

[45]  H. Verbrugh,et al.  Induction of release of tumor necrosis factor from human monocytes by staphylococci and staphylococcal peptidoglycans , 1993, Infection and immunity.

[46]  D. Troost,et al.  Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS. , 1993, Brain : a journal of neurology.

[47]  E. Shevach,et al.  Infection breaks T-cell tolerance , 1992, Nature.

[48]  J. Laman,et al.  New immunoenzyme-cytochemical stainings for the in situ detection of epitope specificity and isotype of antibody forming B cells in experimental and natural (auto) immune responses in animals and man. , 1992, Journal of immunological methods.

[49]  N. Van Rooijen,et al.  Double immunocytochemical staining for in vivo detection of epitope specificity and isotype of antibody-forming cells against synthetic peptides homologous to human immunodeficiency virus-1. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[50]  H. de Visser,et al.  Serum antibodies to peptidoglycan-polysaccharide complexes from the anaerobic intestinal flora in patients with Crohn's disease. , 1990, Digestion.

[51]  F. Wensinck,et al.  Effect of a soluble bacterial carbohydrate fraction on the viscosity of intestinal contents in healthy subjects and patients with Crohn's disease , 1989, European journal of clinical investigation.

[52]  K. Schleifer 5 Analysis of the Chemical Composition and Primary Structure of Murein , 1985 .

[53]  K. Schleifer,et al.  Peptidoglycan Types of Bacterial Cell Walls and Their Taxonomic Implications , 1973, Bacteriological reviews.