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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Induction of tumor necrosis factor- alpha secretion and toll-like receptor 2 and 4 mRNA expression by genital mucosal fluids from women with bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is associated with complications of pregnancy and increased susceptibility to human immunodeficiency virus (HIV) sexual transmission. METHODS: The ability of genital mucosal fluids from women with BV and of microbial flora associated with BV to induce tumor necrosis factor (TNF)- alpha secretion and Toll-like receptor (TLR) 2 and TLR4 mRNA expression was assessed. RESULTS: Primary peripheral-blood mononuclear cells and THP-1 monocytic cells secreted TNF- alpha in response to cervicovaginal lavage (CVL) samples from women with BV. Mycoplasma hominis and Gardnerella vaginalis also stimulated TNF- alpha secretion. Strikingly, CVL samples from women with BV induced up to 60-fold increases in TLR4 mRNA expression, compared with CVL samples from women without BV and with bacteria not associated with BV. Anti-TNF- alpha antibody blocked increases in TLR4 mRNA expression induced by CVL samples from women with BV, indicating that TNF- alpha plays a critical role in induction of TLR4. Both TLR2 and TLR4 mRNA expression were approximately 60-fold higher in cells isolated from the lumen of the genital tract than in cervical mucosal tissue, but lumen TLR mRNA levels did not change significantly after BV treatment. CONCLUSIONS: These experiments show that genital mucosal fluids and certain bacteria from women with BV stimulate TNF- alpha secretion and TLR4 mRNA expression, suggesting mechanisms whereby BV affects pregnancy and HIV transmission.[1]


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