Th17 Cells and IL-17 in Protective Immunity to Vaginal Candidiasis

Abstract

BackgroundTh17 cells play a major role in coordinating the host defence in oropharyngeal candidiasis. In this study we investigated the involvement of the Th17 response in an animal model of vulvovaginal candidiasis (VVC).MethodsTo monitor the course of infection we exploited a new in vivo imaging technique.Resultsi) The progression of VVC leads to a strong influx of neutrophils in the vagina soon after the challenge which persisted despite the resolution of infection; ii) IL-17, produced by vaginal cells, particularly CD4 T cells, was detected in the vaginal wash during the infection, reaching a maximum 14 days after the challenge; iii) The amount and kinetics of IL-23 in vaginal fluids were comparable to those in vaginal cells; iv) The inhibition of Th17 differentiation led to significant inhibition of IL-17 production with consequent exacerbation of infection; v) An increased production of βdefensin 2 was manifested in cells of infected mice. This production was strongly reduced when Th17 differentiation was inhibited and was increased by rIL-17 treatment.ConclusionsThese results imply that IL-17 and Th17, along with innate antimicrobial factors, have a role in the immune response to vaginal candidiasis.

Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization

“…This is not unexpected, as an array of studies currently support the link between Th17/IL-17A and AMP expression (42)(43)(44). Interestingly, out of all AMPs and treatments tested, only mBD-3 was upregulated, and it was upregulated only in the presence of IL-17A in our ex vivo stimulation experiment.…”

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

“…Interestingly, adaptive cell-mediated or humoral immunity appears to play no role in protection against infection, although certain epitope-specific antibodies characterized as protective antibodies can be used therapeutically against infection (134,135,(150)(151)(152). Another interesting caveat is that while Th17 responses are critical to neutrophil responses at other anatomical sites (oral, bloodstream), the role for Th17 responses in the vaginal neutrophil response is controversial (139,153). The strongest evidence to date has shown that mice deficient in several cytokines encompassing the Th17 axis showed no change in the C. albicans-in-FIG 6 Rat model of Candida-associated denture stomatitis.…”

Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine prospects

“…Recruitment of polymorphonuclear cells to the vagina, cytokine (particularly IL-1b and IL-18) production and activation of the lymphocyte subsets T-helper 1 and (with some controversy) T-helper 17 have been attributed a role in anti-Candida protection (Figure 2). [53][54][55][56][57] Notably, the same mechanisms, if inappropriately or excessively stimulated, cause damage through stimulation of an overwhelming inflammation, hence impairing the anti-Candida defense. 58 The vagina is also a special tolerogenic site as it must accept both constant (the vaginal microbiota) and occasional (semen and fetal) non-self-material.…”