Mice immunized by primary vaginal Candida albicans infection develop acquired vaginal mucosal immunity

Abstract

It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense mechanism against Candida infections of the vagina. However, in an estrogen-dependent murine model of experimental vaginal candidiasis, we recently showed that systemic Candida-specific Th1-type CMI induced by immunization with Candida culture filtrate antigen had no effect on vaginal Candida population levels during the course of a vaginal infection. In the present study, mice given a second vaginal inoculation in the presence of peripheral Candida-specific Th1-type CMI induced by prior vaginal infection had anamnestic-type increased delayed-type hypersensitivity (DTH) responses, concomitant with significantly fewer Candida organisms in the vagina than in primary-infected mice. In addition, organisms in secondary-infected mice were fragmented and superficial penetration into the epithelium was reduced. The systemic presence of Candida-specific T suppressor (Ts) cells that significantly suppressed the infection-derived anamnestic DTH reactivity did not abrogate the protective effect in the vagina. Additional experiments showed that vaginally immunized mice were not protected from gastrointestinal or systemic candidiasis and, in contrast to mice with a second vaginal infection, did not demonstrate anamnestic DTH reactivity. These results suggest that a moderate level of local protection against a Candida vaginal infection can be achieved by vaginal immunization but that the protective role of acquired peripheral Candida-specific Th1-type reactivity at the vaginal mucosa appears to be limited.

Oral diseases, mycology and periodontal microbiology of HIV‐1‐infected women

“…Cell-mediated immune responses are believed to be critical for protection against oral candidiasis (10,17,42,46,59). Unlike vaginal candidiasis in which humoral immunity is believed to play a protective role (5,21,22), there are no obvious defects in the mucosal secretory IgA response of HIV-1-infected or AIDS patients that would account for the presence of oral candidiasis (13). Taken together with reports in the literature, our results suggest that cell-mediated immune function critical for protection against oral candidiasis is altered even before a marked decrease in CD4* T lymphocyte numbers is apparent in some HIV-1-seropositive women.…”

Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine prospects

“…In both animal models, recovery from a primary infection provides protection against a subsequent infection. 28,29 Although this typically does not occur in women, the animal models may be useful to study anti-candidal immunity following vaccination (see below).…”

Circulating CD4 and CD8 T cells have little impact on host defense against experimental vaginal candidiasis

“…For experiments investigating the effects of circulating CD4 and CD8 cells on secondary vaginal infections, animals were first given a primary vaginal inoculation in the absence of estrogen treatment (4). At consecutive weeks following inoculation, randomly selected mice were monitored for DTH and vaginal fungal burden in order to establish that DTH had been induced and that the vaginal infection had cleared spontaneously as shown previously (4).…”

“…To study potential host defense mechanisms which provide protection against C. albicans vaginitis more closely, we used an estrogen-dependent murine model of experimental vaginal candidiasis. To date, our studies have shown (i) that a local vaginal C. albicans infection stimulates Candida-specific systemic Th1-type CMI (5,6), (ii) that preinduced Candidaspecific CMI expressed systemically does not protect mice against a vaginal C. albicans infection (7), (iii) that suppression of vaginal infection-induced Candida-specific delayed-type hypersensitivity (DTH) does not enhance the vaginal C. albicans burden (7), (iv) that the spontaneous resolution of a primary vaginal infection results in partial protection from a second vaginal infection, and (v) that this vaginal protection is retained when Candida-specific DTH is suppressed (4).…”