Persistent colonization and transient suppression of DTH responses in an estrogen-dependent vaginal candidosis murine model.

Recurrence of vaginal candidosis in women of childbearing age has been attributed to several predisposing factors including the presence of significant amounts of estrogen in the reproductive tract. In this study, the effect of estrogen on the level of C. albicans colonization, persistence of infection and suppression of DTH responses was investigated in an estrogen-dependent vaginal candidosis murine model. Mice were first injected subcutaneously with 0.5 mg of estradiol valerate 72 hours prior to C. albicans intravaginal inoculation and at weekly intervals thereafter for a period of up to 4 weeks; the inoculum consisted of 2 x 10(7) stationary-phase C. albicans blastoconidia in a volume of 20 microl. C. albicans colonization was evaluated in the spleen, liver, kidney, small intestine and reproductive tract of estrogen-treated and control mice 72 hours following inoculation, DTH responses were evaluated 2 and 5 weeks following primary inoculation and persistence of infection was evaluated at days 2, 3, 4, 8, 12, 19 and 26 post inoculation. Estrogen-treated mice exhibited higher levels of C. albicans colonization compared with control mice; this was most evident in the small intestine and reproductive tract. Estrogen treatment resulted in pronounced suppression of C. albicans-specific DTH responses; in that average footpad swelling was 4.7 mm in untreated mice compared with 2.3 mm in estrogen-treated mice. Long-term estrogen treatment resulted in the persistence of infection; in contrast, C. albicans infection resolved by day 8 post inoculation in untreated mice. DTH responses assayed 5 weeks post primary inoculation in treated mice were on average 4.1 mm, this was similar to that observed in untreated mice tested for DTH response 2 and 5 weeks post primary inoculation. These results suggest that, on the one hand, estrogen has an enhancing effect on C. albicans colonization and persistence of infection. On the other, estrogen seems to suppress DTH responses within the first 2 weeks post infection; persistence of infection under the influence of estrogen, however, seems to coexist with detectable systemic cell-mediated immunity.