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

• Published in: Journal of neurochemistry Vol. 102; no. 6; pp. 2049 - 2060
• Main Authors: Goos, Miriam, Lange, Peter, Hanisch, Uwe-Karsten, Prinz, Marco, Scheffel, Jörg, Bergmann, Reiner, Ebert, Sandra, Nau, Roland
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.09.2007; Blackwell Publishing Ltd; Blackwell
• Subjects: Adult; Aged; Animals; Animals, Newborn; Bacteria; Bacterial diseases; Bacterial diseases of the nervous system. Bacterial myositis; Biochemistry; Biological and medical sciences; Cell culture; Cells; Cells, Cultured; cytosine-guanosine oligodesoxynucleotide; Drug Synergism; Encephalitis - cerebrospinal fluid; Encephalitis - immunology; Encephalitis - microbiology; endotoxin; Female; Fibronectins - cerebrospinal fluid; Fibronectins - pharmacology; Human bacterial diseases; Humans; Immunity, Innate - immunology; Infectious diseases; Inflammation Mediators - pharmacology; Male; Medical sciences; Meningitis; Meningitis, Bacterial - cerebrospinal fluid; Meningitis, Bacterial - immunology; Meningitis, Bacterial - physiopathology; Mice; Mice, Inbred C57BL; Mice, Knockout; microglia; Middle Aged; Molecules; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Nerve Degeneration - immunology; Nerve Degeneration - microbiology; Nerve Degeneration - physiopathology; neuroglia; Neurology; Neurons; Neurosciences; nitric oxide; Nitric Oxide - metabolism; Peptides; Proteins; Rodents; Toll-Like Receptors - agonists; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism; tripalmytoyl-cysteinyl-seryl-(lysyl)3-lysine; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism; Cell culture; Multiple sclerosis; Neuroglia; Cerebrospinal fluid; Inflammatory disease; tumor necrosis factor-alpha; Primary culture; Lipopolysaccharide; Extracellular matrix; microglia; Release; Biological receptor; Immune system; Nervous system diseases; nitric oxide; Cytokine; Rodentia; Stimulator; Inflammation; Protein; Infection; Vertebrata; Mammalia; Bacterial meningitis; Mouse; cytosine-guanosine oligodesoxynucleotide; tripalmytoyl-cysteinyl-seryl- (lysyl)3-lysine; Central nervous system disease; Bacteriosis; endotoxin
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04683.x

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 μg/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.