History and new insights into host defense against vaginal candidiasis

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Abstract

Recurrent vulvovaginal candidiasis (RVVC), caused by Candida albicans, remains a significant problem in women of childbearing age. Although cell-mediated immunity is considered the predominant host defense mechanism against mucosal candidal infections, two decades of research using animal models and results from clinical studies have revealed that adaptive immunity does not play a protective role against VVC owing to putative immunoregulatory mechanisms. Moreover, natural protective mechanisms and factors associated with susceptibility to infection have remained elusive until recently; use of a live challenge model in humans revealed that protection against vaginitis coincides with a non-inflammatory innate presence, whereas symptomatic infection correlates with a neutrophil infiltrate in the vaginal lumen and elevated fungal burden. Therefore, instead of RVVC being caused by a putative deficient adaptive immune response, it is now being considered that symptomatic vaginitis is caused by an aggressive innate response.

Section snippets

Review of protective mechanisms against vaginal candidiasis

Mucosal candidiasis includes oropharyngeal, esophageal, gastrointestinal and vaginal infections. Before the AIDS epidemic, all mucosal sites were considered equally susceptible to infection. Therefore, early hypotheses for studies involving susceptibility to primary RVVC were derived from this broad definition. Accordingly, because mucosal candidiasis occurred most frequently in those patients with T cell immunosuppression 5, 6, 7 and experimental models showed a strong role for T cells in

Many questions left unanswered

Although numerous studies have been conducted over the past two decades to identify the protective host defense mechanisms that are used against vaginitis, what actually protects women from vaginitis and what events occur or are associated with acute or recurrent symptomatic infection are still not understood. These issues, along with several other facts and myths regarding vaginitis, are highlighted in a recent review by Mardh et al. [64]. The clinical studies and animal models have, however,

Development of a human live challenge model

In light of all the findings to date, we reasoned that the experimental design that would probably provide the most valuable information regarding putative vaginal protective host defenses against C. albicans was a live challenge model that offers controlled but natural conditions under which immunoreactivity can be properly monitored. Live challenge models in humans are not new. Currently there are live challenge models for Haemophilus ducreyi and Neisseria gonorrheae 66, 67. The primary

Concluding remarks

There has been an extensive history of studies that have attempted to understand the pathogenesis of VVC and RVVC, as well as the natural protective immune mechanisms against the infection. All the studies, both clinical and using animal models, have had an impact on our understanding of the complex events that are associated with protection and susceptibility to vaginitis. However, although the studies using animal models and clinical studies of women with RVVC have been invaluable, it has

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