Candida-specific Th1-type responsiveness in mice with experimental vaginal candidiasis

Abstract

The role of systemic cell-mediated immunity (CMI) as a host defense mechanism in the vagina is poorly understood. Using a murine pseudoestrus model of experimental vaginal candidiasis, we previously found that animals given a vaginal inoculum of viable Candida albicans blastoconidia acquired a persistent vaginal infection and developed Candida-specific delayed-type hypersensitivity (DTH) responses. The present study was designed to characterize the peripheral CMI reactivity generated from the vaginal infection in mice and to determine whether pseudoestrus is a prerequisite for the induction of peripheral CMI reactivity. Mice treated or not treated with estrogen and given a vaginal inoculum of C. albicans blastoconidia were examined for 4 weeks for their vaginal Candida burden and peripheral CMI reactivity, including DTH responsiveness and in vitro Thl (interleukin-2 [IL-21, gamma interferon [IFN'yJ)/Th2 (IL-4, IL-10)-type lymphokine production in response to Candida antigens. Results showed that although mice not treated with estrogen before being given a vaginal inoculum of C. albicans blastoconidia developed only a short-lived vaginal infection and harbored significantly fewer Candida CFU in the vagina compared with those given estrogen and then infected; DTH reactivity was equivalent in both groups. In vitro measurement of CMI reactivity further showed that lymph

Immunoresponses in dermatomycoses

“…Antigen Presenting Cells response involving cells producing interferon (IFN)-c, with Th2 responses leading to increased susceptibility to C. albicans infection in IFN-c receptor-deficient mice. [41][42][43][44][45] However, the findings in OPC mouse models showed inconsistencies in the theory, as IL-12p40 À/À and not IFN-c À/À mice were susceptible to Candida, indicating that the immune responses may rely more on Th17 cells that produce IL-17A, a population distinct from Th1/Th2 cells. IL-23, a dimeric cytokine composed of IL-12p40 and IL-23p19, plays an important role in the maintenance, expansion and downstream effector functions of Th17 cells, which explains the important findings of Candida susceptibility in IL-12p40 À/À mice which were at first attributed to Th1.…”

Estrogen‐dependent induction of persistent vaginal candidosis in naïve mice

“…Non-germ free female (12)(13)(14) week old) Balb/c mice raised at the Hashemite University vivarium were used throughout the study. Mice were treated with estrogen on weekly basis by subcutaneous administration of 0.5 mg estradiol valerate dissolved in 0.1 ml sesame oil (Schering, Berlin, Germany).…”

“…8,11,12 Several investigators have used estrogen in conjunction with C. albicans vaginal inoculation to construct animal models of persistent VC; among these models is the estrogen-dependent VC (EDVC) murine model. [13][14][15] This model has proved to be useful in evaluating the various aspects of pathogenesis of VC as VC in the absence of estrogen treatment in the murine system is transient and only lasts for few days. 14 Among the several important findings obtained using this model was the observation that estrogen treatment results in persistent VC that it results in suppressed delayed type hypersensitivity (DTH) responses 15 and that it leads to a significant increase in vaginal T lymphocyte numbers especially the numbers of CD8 + T cells.…”

“…[13][14][15] This model has proved to be useful in evaluating the various aspects of pathogenesis of VC as VC in the absence of estrogen treatment in the murine system is transient and only lasts for few days. 14 Among the several important findings obtained using this model was the observation that estrogen treatment results in persistent VC that it results in suppressed delayed type hypersensitivity (DTH) responses 15 and that it leads to a significant increase in vaginal T lymphocyte numbers especially the numbers of CD8 + T cells. 16,17 These findings strongly point to the possibility that VC and RVC can be directly correlated with the presence of elevated levels of estrogen in the reproductive tract; this may apply irrespective of the immune status of the host or the contribution of other possible predisposing factors.…”

Suppression of Anti‐Candida Activity of Murine Neutrophils by Progesterone In Vitro: A Possible Mechanism in Pregnant Women's Vulnerability to Vaginal Candidiasis

“…None of these factors, however, has been proved to be responsible for predisposing the host to this condition. Recently, it was demonstrated in murine models of vaginal candidiasis that growth and persistence of C. albicans cells in vaginal tissues is controlled by the immune system, especially cell-mediated immunity in which various cytokines augment host-defense mechanisms against Candida infection (9).…”