Anticandidal immunity and vaginitis: novel opportunities for immune intervention

The majority of human Candida infections occur at a mucosal surface. One of these infections, vulvovaginal candidiasis (VVC), is a widespread, common disease affecting a large proportion of otherwise healthy women. Some women undergo recurrent forms of VVC (RVVC); in these cases the quality of life is devastated, the associated cost of medical visits is high, there is substantial use of unprescribed therapy, and there is a possible increase in drug resistance. However, relatively little is known about the pathogenic and immunoregulatory mechanisms underlying VVC and RVVC. While there is consensus that local rather than systemic factors play a decisive role in controlling the infection, there is no consensus about the nature of the local factors. The results obtained with animal models and human investigations have not provided an overall consistent picture; rather, they have generated divergent interpretations about the role of innate and adaptive immunity against vaginal infection. Nonetheless, recent experimental evidence has resulted in some optimism concerning the challenge of clarifying the immunological basis of susceptibility to, and protection from, vaginal candidiasis through the development of appropriate immune interventions to integrate with or even replace antifungal chemotherapy. The aim of this review is to provide a short update of the evidence mentioned above and the resulting optimism. Here, we critically consider the linkage between the virulence traits of the fungus and the host responses to these traits, two interrelated aspects which have rarely been treated together in other reviews of the topic (36, 39-41, 48, 54, 56, 57, 65, 66, 74, 94, 102). On this basis, we suggest that despite substantial belief to the contrary, novel tools derived from adaptive immunity, in particular virulence-neutralizing antibodies (Abs), may become part of the anti-Candida armamentarium to fight vaginal infection