Background:  Worldwide, bacterial vaginosis is highly prevalent among women of childbearing age and has been associated with an increased risk for HIV acquisition and preterm childbirth. The mechanisms of bacterial vaginosis effects on the host have not been elucidated. Bacterial vaginosis is an alteration in normal vaginal flora with decreased numbers of lactobacilli and increased numbers of other bacteria. Dendritic cells (DC) located at mucosal surfaces sample the environment to sense infectious agents, and mature into antigen presenting cells when exposed to “danger” signals, such as lipopolysaccharide. DC are also implicated in HIV acquisition. Since bacterial vaginosis flora or normal flora may contain danger signals, we examined the effect of mucosal fluid from women with bacterial vaginosis or normal flora on DC function.

Methods:  Cervicovaginal lavage (CVL) samples were obtained from women and evaluated for bacterial vaginosis using the Nugent criteria. Monocyte-derived dendritic cells (MDDC) or plasmacytoid dendritic cells (pDC) from healthy donors were exposed to CVL samples from women with normal flora (normal CVL) or bacterial vaginosis. After CVL exposure, interleukin-12 (IL-12) secreted by MDDC was measured by ELISA; cell surface markers on DC were determined by flow cytometry; endocytic ability was measured by FITC-dextran uptake; and allogeneic mixed lymphocyte reaction assessed antigen presentation. Mann Whitney test was used to determine significance.

Results:  IL-12 production by MDDC was significantly higher following incubation with bacterial vaginosis CVL (12.1 ng/mL) versus normal CVL (1.2 ng/mL, p <0.001). The maturation markers HLA-DR, CD40, and CD83 on MDDC incubated with bacterial vaginosis CVL were significantly higher (54, 62, and 57% of lipopolysaccharide) than those incubated with CVL from women with normal flora (9, 22, 29%, p ≤0.03). MDDC exposed to bacterial vaginosis CVL had decreased endocytic ability (8% FITC-Dextran vs 26% for normal CVL) and induced increased proliferation of T cells in allogeneic MLR (42% vs 9%). The level of co-stimulatory marker CD86 was significantly higher on pDC following incubation with bacterial vaginosis CVL (156% of CPG) versus normal CVL (17%, p <0.001). CVL samples from women with normal vaginal flora did not induce a significant change for any of the tested parameters compared to medium treated MDDC or pDC.

Conclusions:  The change in activation and maturation status of DC induced by mucosal fluid from bacterial vaginosis suggests that bacterial vaginosis has a dramatic effect on local dendritic cell function in vivo and points to a mechanism through which bacterial vaginosis may affect HIV acquisition and local host immunity.