The study of cell-mediated immune response in recurrent vulvovaginal candidiasis

Nawrot, Urszula; Grzybek-Hryncewicz, K; Zielska, U.; Czarny, Anna; Podwińska, J

doi:10.1111/j.1574-695x.2000.tb01509.x

Cited by 21 publications

(9 citation statements)

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“…Despite known risk factors such as the hormonal status, diabetes, pregnancy or immunosuppressive therapy (Milsom and Forssman, 1985; Sobel, 1985,1993; Kent, 1991; Nawrot et al, 2000), the majority of the patients are healthy women who are not exposed to these conditions. In the present study, we explored whether genetic variation in genes coding for PRRs involved in Candida recognition (Jouault et al, 2003) affects susceptibility to RVVC.…”

Section: Discussionmentioning

confidence: 99%

Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis

Rosentul¹,

Delsing²,

Jaeger³

et al. 2014

Front. Microbiol.

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Objective: Approximately 5% of women suffer from recurrent vulvovaginal candidiasis (RVVC). It has been hypothesized that genetic factors play an important role in the susceptibility to RVVC. The aim of this study was to assess the effect of genetic variants of genes encoding for pattern recognition receptors (PRRs) on susceptibility to RVVC.Study design: For the study, 119 RVVC patients and 263 healthy controls were recruited. Prevalence of polymorphisms in five PRRs involved in recognition of Candida were investigated in patients and controls. In silico and functional studies were performed to assess their functional effects.Results: Single nucleotide polymorphisms (SNPs) in TLR1, TLR4, CLEC7A, and CARD9 did not affect the susceptibility to RVVC. In contrast, a non-synonymous polymorphism in TLR2 (rs5743704, Pro631His) increased the susceptibility to RVVC almost 3-fold. Furthermore, the TLR2 rs5743704 SNP had deleterious effects on protein function as assessed by in silico analysis, and in vitro functional assays suggested that it reduces production of IL-17 and IFNγ upon stimulation of peripheral blood mononuclear cells with Candida albicans. No effects were observed on serum mannose-binding lectin concentrations.Condensation: This study demonstrates the association of susceptibility to RVVC with genetic variation in TLR2, most likely caused by decreased induction of mucosal antifungal host defense.Conclusion: Genetic variation in TLR2 may significantly enhance susceptibility to RVVC by modulating host defense mechanisms against Candida. Additional studies are warranted to assess systematically the role of host genetic variation for susceptibility to RVVC.

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Section: Discussionmentioning

confidence: 99%

Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis

Rosentul¹,

Delsing²,

Jaeger³

et al. 2014

Front. Microbiol.

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“…However, comprehensive testing of women with RVVC showed no demonstrable deficiency in Candida ‐specific Th1‐type CMI 15 . And although other sporadic reports challenged this, 16–18 the general consensus became that systemic immunity was not playing a dominant role at the vaginal mucosa and that the immune deficiency in women with primary RVVC resided locally. This was supported by several clinical observations.…”

Section: Review Of Immune Reactivity Against Vaginal Candidiasismentioning

confidence: 99%

History and Update on Host Defense Against Vaginal Candidiasis

Fidel

2006

American J Rep Immunol

147

130

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Vulvovaginal candidiasis (VVC), caused by Candida albicans, remains a significant problem in women of childbearing age. While cell-mediated immunity is considered the predominant host defense mechanism against mucosal candidal infections, two decades of research from animal models and clinical studies have revealed a lack of a protective role for adaptive immunity against VVC caused by putative immunoregulatory mechanisms. Moreover, natural protective mechanisms and factors associated with susceptibility to infection have remained elusive. That is until recently, when through a live challenge model in humans, it was 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. Thus, instead of VVC being caused by a putative deficient adaptive immune response, it is now being considered that symptomatic vaginitis is caused by an aggressive innate response.

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“…The immune response elicited during an episode of RVVC differs from the classical host defense mechanism, as infection occurs despite normal Candida-specific Th1-type cellmediated immunity (9,16). Protection from RVVC is believed to be acquired locally, possibly involving incompletely defined vaginal epithelial carbohydrate adhesion molecules (2,24).…”

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confidence: 99%

Increased Susceptibility of Secretor Factor Gene Fut2 -Null Mice to Experimental Vaginal Candidiasis

Hurd

Domino

2004

Infect Immun

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Fut2-LacZ-null mice, which are a model of the human ABO and Lewis nonsecretor group, display increased susceptibility to experimental yeast vaginitis, indicating a role for ␣(1,2)fucosylated cervical glycans in mucosal defense. However, the lack of significant effect of competitive inhibition by exogenous neoglycoproteins in this study emphasizes the complexity of Candida-epithelial cell adhesion events.Recurrent vulvovaginal candidiasis (RVVC) is a mucosal infection caused by the opportunistic fungus Candida albicans which affects up to 5 to 10% of women of reproductive age (22,23). The immune response elicited during an episode of RVVC differs from the classical host defense mechanism, as infection occurs despite normal Candida-specific Th1-type cellmediated immunity (9, 16). Protection from RVVC is believed to be acquired locally, possibly involving incompletely defined vaginal epithelial carbohydrate adhesion molecules (2, 24).A common null mutation within the coding region of the ␣(1,2)fucosyltransferase gene, FUT2 (secretor factor gene), leads to ABO and Lewis histo-blood group antigen nonsecretion from mucosal tissues in approximately 20% of humans, with ethnic variation (13,14). Nonsecretor status has been associated with differences in susceptibility to several infections, including infections with Norwalk virus (15), human immunodeficiency virus (1), Escherichia coli (17, 21), Staphylococcus aureus (20), Campylobacter jejuni (19), calicivirus (18), and C. albicans (5). While the mechanism of how C. albicans interacts with nonsecretors is not known, a host-microbe adhesion mechanism is supported by in vitro studies that have demonstrated binding of various fucosylated oligosaccharides to germ tubes of C. albicans (3,4,6,25). We report here the development of a mouse model for the nonsecretor phenotype to test the importance of ␣(1,2)fucosylated glycans in vivo during experimental vaginal candidiasis.Absence of endocervical and vaginal ␣(1,2)fucosylated glycans in Fut2-LacZ-null mice. The expression pattern of Fut2 and resulting ␣(1,2)fucosylated glycans in the female lower reproductive tract was examined in 8-to 10-week-old female mutant mice (Fut2-LacZ-null mice) that contained a targeted replacement of the Fut2 open reading frame with a bacterial lacZ reporter gene (8). The original mutant mice were backcrossed 10 generations to C57BL/6J mice (Jackson Laboratory, Bar Harbor, Maine), and the resulting congenic strain used for this study was designated B6.129X1-Fut2 tm1Sdo (MGI accession ID no. 2183220). A second line of mutant mice lacking the coding region of another ␣(1,2)fucosyltransferase gene, Fut1, was similarly backcrossed for 10 generations to C57BL/6J mice and was designated B6.129X1-Fut1 tm1Sdo (MGI accession ID no. 2183219) and used as genetic background controls.Using a 5-bromo-4-chloro-3-indolyl␤-D-glucuronic acid (XGal) staining method (7), specific nuclear LacZ staining was detected in the glandular and lumenal epithelium of the endocervix of Fut2-LacZ-null mice in estrus (Fig. 1A), but ...

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The study of cell-mediated immune response in recurrent vulvovaginal candidiasis

Cited by 21 publications

References 22 publications

Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis

Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis

History and Update on Host Defense Against Vaginal Candidiasis

Increased Susceptibility of Secretor Factor Gene Fut2 -Null Mice to Experimental Vaginal Candidiasis

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