Oral and vaginal epithelial cell anti‐<i>Candida</i> activity is acid labile and does not require live epithelial cells

The prevalence of oropharyngeal candidiasis continues to be high, mainly because of an increasing population of immunocompromised patients. Traditional treatment of oropharyngeal candidiasis has relied on the use of antimicrobial drugs. However, unsatisfactory results with drug monotherapy and the emergence of resistant strains have prompted investigations into the potential use of adjunctive immunoenhancing therapies for the treatment of these infections. Here we review the host-recognition systems of Candida albicans, the immune and inflammatory response to infection, and antifungal effector mechanisms. The potential of immune modulation as a therapeutic strategy in oropharyngeal candidiasis is also discussed.

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“…However, more recent work showed that the antifungal activity is actually due to an acid-labile protein moiety (Ref. 112) (Fig. 1).…”

Section: Immune and Nonimmune Antifungal Effector Cells In The Oral Mmentioning

confidence: 97%

Immune defence mechanisms and immunoenhancement strategies in oropharyngeal candidiasis

Villar

Dongari-Bagtzoglou

2008

Expert Rev. Mol. Med.

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“…In vaginal and oral epithelial cells, the mechanism of action involved direct cell contact with Candida but no role for soluble factors [61, 64]. In addition, the antifungal activity was fungistatic rather than fungicidal, which could be elicited by intact, not necessarily live, epithelial cells [65]. We recently reported our discovery that a likely candidate for this anti- Candida activity is Annexin A1, a molecule expressed on the surface of epithelial cells and known to be involved in regulating growth pathways in C. albicans [66].…”

Section: Paradigm Shift For Vvc – Role For Innate Immunitymentioning

confidence: 99%

Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins

2012

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Vulvovaginal candidiasis (VVC), caused by Candida albicans, affects a significant number of women during their reproductive years. More than two decades of research have been focused on the mechanisms associated with susceptibility or resistance to symptomatic infection. Adaptive immunity by Th1-type CD4+ T cells and downstream cytokine responses are considered the predominant host defense mechanisms against mucosal Candida infections. However, numerous clinical and animal studies have indicated no or limited protective role of cells and cytokines of the Th1 or Th2 lineage against vaginal infection. The role for Th17 is only now begun to be investigated in-depth for VVC with results already showing significant controversy. On the other hand, a clinical live-challenge study and an established animal model have shown that a symptomatic condition is intimately associated with the vaginal infiltration of polymorphonuclear leukocytes (PMNs) but with no effect on vaginal fungal burden. Subsequent studies identified S100A8 and S100A9 Alarmins as key chemotactic mediators of the acute PMN response. These chemotactic danger signals appear to be secreted by vaginal epithelial cells upon interaction and early adherence of Candida. Thus, instead of a putative immunodeficiency against Candida involving classical immune cells and cytokines of the adaptive response, the pathological inflammation in VVC is now considered a consequence of a non-productive innate response initiated by non-classical immune mediators.

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“…In fact, several forms of immunoregulation seem to be in place to inhibit such responses (11,19,26). Instead, innate immunity by epithelial cells appears to provide some level of protection through noninflammatory processes involving direct contact with Candida (3,29,39). To further investigate factors associated with susceptibility to infection, a human live challenge was established where healthy women were given an intravaginal inoculation of C. albicans and followed for the natural history of infection (10).…”

mentioning

confidence: 99%

Epithelial Cell-Derived S100 Calcium-Binding Proteins as Key Mediators in the Hallmark Acute Neutrophil Response duringCandidaVaginitis

et al. 2010

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Vulvovaginal candidiasis (VVC), caused by Candida species, is a significant problem in women of childbearing age. Similar to clinical observations, a robust vaginal polymorphonuclear neutrophil (PMN) migration occurs in a subset of mice without affecting vaginal fungal burden. We hypothesize that the vaginal PMN infiltrate and accompanying inflammation are not protective but instead are responsible for the symptoms of infection. The purpose of this study was to identify the signal(s) associated with the PMN response in the established mouse model. Vaginal lavage fluid from inoculated mice were categorized base on PMN counts, evaluated for PMN chemotactic activity and analyzed by SDS-PAGE and mass spectrometry (MS) for unique protein identification. The lavage fluid from inoculated mice with high, but not low, PMN levels showed increased chemotactic activity. Likewise, SDS-PAGE of lavage fluid with high PMN levels showed distinct protein patterns. MS revealed that bands at 6 and 14 kDa matched the PMN chemotactic calcium-binding proteins (CBPs), S100A8 and S100A9, respectively. The presence of the CBPs in lavage fluid was confirmed by Western blots and enzyme-linked immunosorbent assay. Vaginal tissues and epithelial cells from inoculated mice with high PMN levels stained more intensely and exhibited increased mRNA transcripts for both proteins compared to those in mice with low PMN levels. Subsequent antibody neutralization showed significant abrogation of the chemotactic activity when the lavage fluid was treated with anti-S100A8, but not anti-S100A9, antibodies. These results reveal that the PMN chemotactic CBP S100A8 and S100A9 are produced by vaginal epithelial cells following interaction with Candida and that S100A8 is a strong candidate responsible for the robust PMN migration during experimental VVC.Vulvovaginal candidiasis (VVC), caused by Candida species, is an opportunistic fungal infection that affects ca. 75% of healthy women of childbearing age (34). Menarchal women are predisposed to VVC through several exogenous factors, most of which involve elevated hormone levels (e.g., pregnancy, use of high estrogen oral contraception or hormone replacement therapies, and the luteal phase of the menstrual cycle) (34). Frequent antibiotic usage and uncontrolled diabetes mellitus are also known to be linked to increased susceptibility to VVC. Recurrent vulvovaginal candidiasis (RVVC), defined as three or more episodes of VVC per year, affects a separate 5 to 10% of menarchal women. Most cases of RVVC are primary RVVC, where idiopathic infection occurs with no predisposing factors, whereas secondary RVVC (repeated occurrence of acute VVC) could occur as a result of being unable to avoid certain predisposing factors (34).Although VVC and RVVC have historically been attributed to a putative local immune deficiency, several studies using a mouse model of Candida vaginitis and many cross-sectional clinical studies evaluating women with primary RVVC have shown that protection is not mediated by local or systemic adap...

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Oral and vaginal epithelial cell anti‐Candida activity is acid labile and does not require live epithelial cells

Cited by 30 publications

References 16 publications

Immune defence mechanisms and immunoenhancement strategies in oropharyngeal candidiasis

Immune defence mechanisms and immunoenhancement strategies in oropharyngeal candidiasis

Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins

Epithelial Cell-Derived S100 Calcium-Binding Proteins as Key Mediators in the Hallmark Acute Neutrophil Response duringCandidaVaginitis

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