title: Fibronectin is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis and enhances inflammation caused by bacterial products in primary mouse microglial cell cultures.
abstract: Toll-like receptors (TLR) play a key role in the recognition of pathogenic organisms. Fibronectin, an extracellular matrix protein, is considered a potent stimulator of the innate immune system through TLR4. In bacterial meningitis, several extracellular matrix proteins and bacterial compounds are elevated in the CSF. For this reason, we hypothesized that these molecules may jointly stimulate the innate immune system and increase neuronal damage in bacterial meningitis. Concentrations of fibronectin were elevated in the CSF of patients suffering from bacterial meningitis, but not in patients with multiple sclerosis, when compared with control patients without CSF abnormalities. In primary cultures of mouse microglial cells, co-administration of fibronectin at concentrations occurring in the CSF in bacterial meningitis (10 microg/mL) with defined TLR agonists [lipopolysaccharide (TLR4), the synthetic lipopeptide tripalmytoyl-cysteinyl-seryl-(lysyl)3-lysine (TLR2) and single-stranded unmethylated cytosine-guanosine oligodesoxynucleotide (TLR9)] led to an additive release of nitric oxide and tumor necrosis factor-alpha when compared with the release elicited by either compound alone. In conclusion, the inflammatory reaction to bacterial compounds can be aggravated by endogenous fibronectin at elevated levels during bacterial CNS infections. This additive or synergistic effect may contribute to neuronal damage during bacterial meningitis.
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, GermanyDepartment of Neuropathology, Georg-August-University, Göttingen, GermanyDade Behring, Eschborn, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Goos
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, GermanyDepartment of Neuropathology, Georg-August-University, Göttingen, GermanyDade Behring, Eschborn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lange
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, GermanyDepartment of Neuropathology, Georg-August-University, Göttingen, GermanyDade Behring, Eschborn, Germany.
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, GermanyDepartment of Neuropathology, Georg-August-University, Göttingen, GermanyDade Behring, Eschborn, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, GermanyDepartment of Neuropathology, Georg-August-University, Göttingen, GermanyDade Behring, Eschborn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Scheffel
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, GermanyDepartment of Neuropathology, Georg-August-University, Göttingen, GermanyDade Behring, Eschborn, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Bergmann
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, GermanyDepartment of Neuropathology, Georg-August-University, Göttingen, GermanyDade Behring, Eschborn, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ebert
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, GermanyDepartment of Neuropathology, Georg-August-University, Göttingen, GermanyDade Behring, Eschborn, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004357:Drug Synergism; D004660:Encephalitis / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005353:Fibronectins / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D018836:Inflammation Mediators / Q000494:pharmacology; D008297:Male; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009410:Nerve Degeneration / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005353:Fibronectins; D018836:Inflammation Mediators; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide