Dendritic cell activation and maturation induced by mucosal fluid from women with bacterial vaginosis

Abstract

Dendritic cells (DC) at mucosal surfaces mature when exposed to "danger" signals such as LPS. Bacterial vaginosis (BV) is a prevalent alteration of the vaginal bacterial flora associated with preterm childbirth and increased risk for HIV acquisition. We examined the effect of mucosal fluid from women with BV or healthy flora on DC function. IL-12, IL-23 and p40 production by monocytederived dendritic cells (MDDC) were all induced by BV samples. Activation/maturation markers HLA-DR, CD40, and CD83 on MDDC incubated with BV CVL were also induced. BV CVL also decreased the endocytic ability of MDDC and increased proliferation of T-cells in allogeneic MLR. Plasmacytoid dendritic cell (pDC) CD86 expression was induced by BV CVL. Healthy flora CVL had little effect in any of the tests. This study suggests that BV, but not healthy flora, affects local dendritic cell function in vivo suggesting a mechanism through which BV affects mucosal immunity.

Cervicovaginal Levels of Proinflammatory Cytokines Are Increased During Chlamydial Infection in Bacterial Vaginosis But Not in Lactobacilli-Dominated Flora

“…Because increased IL-6 and IL-8 levels are only found in women with BV and not in women with normal flora, it indicates that, of the former two possibilities, the production site of these cytokines rather is the vagina and not the endocervix. In fact, studies already showed that vaginal fluids from women with BV are more stimulatory on activating the cytokine cascade in vitro when compared to vaginal contents from the normal flora [30,31]. Finally, the current findings showing that levels of proinflammatory cytokines are unchanged in the normal flora, even in the presence of CT, reinforcing the importance of maintaining a lactobacillidominated vaginal flora for protecting against STI acquisition.…”

Microbiome, sex hormones, and immune responses in the reproductive tract: Challenges for vaccine development against sexually transmitted infections

“…Certain bacterial products, particularly from anaerobes, have been shown to result in induction of proinflammatory cytokine production through TLR stimulation [79], dendritic cell activation and maturation,[80] and immune cell migration, apoptosis, and phagocytosis through the production of specific short-chain fatty acids. [81] G. vaginalis , a facultative anaerobe, has been shown to produce sialidases, which are capable of inactivating local IgA.…”

Immune Responses to HIV in the Female Reproductive Tract, Immunologic Parallels with the Gastrointestinal Tract, and Research Implications

“…St. John and colleagues compared the effects of vaginal fluid from women with bacterial vaginosis or healthy controls on monocyte-derived dendritic cells. Fluids from women with bacterial vaginosis, but not controls, induced production of IL-12, IL-23, increased expression of dendritic cell activation markers (HLA-DR, CD40 and CD83) and stimulated proliferation of T-cells in allogeneic mixed lymphocyte reactions41. Chancroid is one of the STDs most closely associated with HIV transmission, perhaps due to extensive disruption of the epithelial barrier, bleeding and recruitment of susceptible cells42.…”