Effects of preinduced Candida-specific systemic cell-mediated immunity on experimental vaginal candidiasis

Abstract

It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense factor against recurrent vaginal infections caused by Candida albicans. Using an estrogen-dependent murine model of vaginal candidiasis, we have previously shown that mice inoculated vaginally with C. albicans acquire a persistent vaginal infection and develop Candida-specific Thl-type systemic CMI. In the present study, experimental vaginitis was monitored in the presence of preinduced systemic Candida-specific CMI. Mice immunized systemically with C. albicans culture filtrate antigens (CaCF) in complete Freund's adjuvant (CFA) had Thl-type reactivity similar to that of vaginally infected mice. CaCF given to mice intravenously induced Candida-specific suppressor T (Ts) cells. Mice preimmunized with CaCF-CFA and given a vaginal inoculum of C. albicans had positive delayed-type hypersensitivity (DTH) reactivity from the time of vaginal inoculation through 4 weeks. Conversely, mice infected in the presence of Ts cells had significantly reduced DTH responses throughout the 4-week period in comparison with naive infected mice. However, the presence of Thl-type Candida-specific DTH cells or Ts cells, either induced in mice prior to vaginal inoculation or adoptively transferred at the time of inoculation, had no effect on the vaginal Candida burden through 4 weeks of infection. A similar lack of effects was obtained in animals with lower Candida population levels resulting from a reduction in or absence of exogenous estrogen. These results suggest that systemic Thl-type CMI demonstrable with CaCF is unrelated to protective events at the level of the vaginal mucosa.

Effects of glycyrrhizin, an active component of licorice roots, onCandida albicansinfection in thermally injured mice

“…Non-specific immune responses, expressed by activation of polymorphonuclear neutrophils [28][29][30] and macrophages [31,32], have been shown to be involved in the resistance to the early phase infection with C. albicans. A major influence in host resistance against systemic C. albicans infection is a type 1 T cell-associated cellular response (type 1 T cell response) [33][34][35][36][37][38]. Type 1 T lymphocytes produce type 1 cytokines (IL-2 and IFN-g) following appropriate stimulation [34].…”

“…Type 1 T lymphocytes produce type 1 cytokines (IL-2 and IFN-g) following appropriate stimulation [34]. These type 1 cytokines are able to activate and enhance killing activities of effector cells (cytotoxic T lymphocytes, natural killer cells, macrophages and neutrophils) targeted to cells infected with C. albicans [34][35][36][37][38][39]. However, type 1 T cell responses are generally suppressed by type 2 cytokines (IL-4 and IL-10) [40][41][42] released from T helper type 2 cells (Th2 cells) or CD8 þ type 2 T cells [43][44][45].…”

Rats clearing a vaginal infection by Candida albicans acquire specific, antibody-mediated resistance to vaginal reinfection

“…The rat vaginal model has generally been used in studies assessing antimycotic activity in vivo or potential virulence factors and intravaginal growth characteristics of C. albicans (4,6,19,20,21,23). In a seemingly similar mouse model (not requiring oophorectomy but only estrogen administration), Fidel and collaborators have recently demonstrated the elicitation of systemic C. albicans-specific CMI, particularly of the Th-1 type, in intravaginally infected animals (12)(13)(14). There was no correlation, however, between the level of adaptive anticandidal CMI expressed by lymphocytes of the peripheral blood or lymph nodes and the extent of vaginal infection, suggesting that systemic CMI was probably uncoupled from vaginal immunity (12,14).…”

“…In a seemingly similar mouse model (not requiring oophorectomy but only estrogen administration), Fidel and collaborators have recently demonstrated the elicitation of systemic C. albicans-specific CMI, particularly of the Th-1 type, in intravaginally infected animals (12)(13)(14). There was no correlation, however, between the level of adaptive anticandidal CMI expressed by lymphocytes of the peripheral blood or lymph nodes and the extent of vaginal infection, suggesting that systemic CMI was probably uncoupled from vaginal immunity (12,14). The possible role of antibodies in the infection was not addressed.…”

“…To understand the fungal and host factors involved in the pathogenesis of candidal vaginitis, estrogen-dependent mouse or rat models of vaginal infections have been employed (7,19,23). In particular, using the mouse model, Fidel and collaborators have presented a considerable set of experimental data linking vaginal infection with elicitation of specific, systemic cell-mediated immunity (CMI) to Candida albicans, although this intense CMI response could not be correlated with anti-C. albicans protection mechanisms acting at the vaginal level (12)(13)(14).…”