Vulvovaginal candidiasis (VVC) caused by the commensal organism remains a significant

Vulvovaginal candidiasis (VVC) caused by the commensal organism remains a significant problem among women of childbearing age with protection against and susceptibility to infection still poorly understood. However analysis of draining lymph node DC subsets revealed a predominance of immunoregulation-associated CD11c+ B220+ plasmacytoid DCs (pDCs) under both uninfected and infected conditions. Staining of vaginal DCs showed the presence of both DEC-205+ and pDCs with extension of dendrites into the vaginal lumen of infected mice in close contact with infection and potentially through the action of pDCs. Vulvovaginal candidiasis (VVC) is a significant problem affecting 75% of normal healthy women at least once during their reproductive years (39 40 infections of mucosal tissues (4 33 no protective role for local or systemic CMI has been demonstrated for vaginal infections. Instead it is postulated that a protective adaptive immune response to vaginal infection is prohibited by a local tolerizing condition or immunoregulatory environment at the vaginal mucosa and the draining lymph nodes. This is supported by the presence of CD4+ CD25+ MLN2480 regulatory T cells in the draining lymph nodes (43) γ/δ T cells in the vagina (42) and immunoregulatory cytokines (interleukin-10 [IL-10] and transforming growth factor β [TGF-β]) in the lymph nodes and vaginal tissue (42). Furthermore there is little evidence for Rabbit polyclonal to SEPT4. changes in the percentage or composition of vaginal T-cell populations during experimental vaginal candidiasis (12) suggesting a lack of systemic T-cell infiltration or local T-cell expansion. Immunoregulation at a reproductive site may reflect a means for the host to avoid chronic inflammation to a commensal organism such as in a commensal state and out of a pathogenic condition. Current evidence suggests this involves MLN2480 innate immune mechanisms by epithelial cells (2 10 44 Dendritic cells (DCs) are considered the major antigen-presenting cell MLN2480 (APC) responsible for activation of the adaptive immune response. Recent studies also suggest a role for DCs in the initiation of immunoregulatory events and maintenance of tolerogenic conditions. Different DC subsets appear responsible for each condition: CD11c+ B220+ plasmacytoid DCs (pDCs) are involved in tolerance induction whereas CD11c+ B220? myeloid DCs are involved in the induction of classical inflammatory responses. pDCs have been shown to be the predominant DC population in lymph nodes under tolerizing conditions (28) express low levels of major histocompatibility complex (MHC) class II and costimulatory molecules (24 28 and can induce the differentiation of IL-10-producing Treg cells (5 17 24 37 MLN2480 This is in contrast to the myeloid DCs that express high levels of MHC class II and costimulatory molecules in their activated state and are associated with Th cell activation (24 28 Finally DCs are known to be present in the vaginal mucosa (18-20 41 45 and studies on the interaction of with bone marrow-derived DCs have been reported (1 6 26 31 The purpose of this study was to investigate the presence of DCs in the vagina during infection with and to examine the potential role of DCs in the induction phase of the vaginal immune response to in the vagina that includes the immunoregulatory events using the well-established murine model of experimental vaginal candidiasis. MATERIALS AND METHODS Mice. Female CBA/J (infection. Mice were injected subcutaneously with 100 μl of 0.2 mg/ml estradiol (Sigma Chemical Co. St. Louis MO) in sesame oil 72 h prior to inoculation. Intravaginal inoculation was performed by introducing 20 μl of phosphate-buffered saline (PBS) containing 5 × 104 blastoconidia from a stationary-phase culture (overnight culture at 25°C in Phytone-peptone medium plus 0.1% glucose) into the vagina. MLN2480 Control animals were estrogenized and inoculated with PBS only or PBS containing 5 × 104 heat-killed blastoconidia (incubated at 60°C for 2 h washed and cultured for verification). Separate groups of mice were sacrificed at days 4 and 7 postinoculation. Vaginal lavages were conducted using 100 μl of sterile PBS with repeated aspiration for 30 to 40 s and the fluid was cultured at 1:10 serial dilutions on Sabouraud-dextrose.