Induction of Tumor Necrosis Factor–α Secretion and Toll‐Like Receptor 2 and 4 mRNA Expression by Genital Mucosal Fluids from Women with Bacterial Vaginosis

Abstract

Bacterial vaginosis (BV) is associated with complications of pregnancy and increased susceptibility to human immunodeficiency virus (HIV) sexual transmission. 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. 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. 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.