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Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (pANCA) Impair Neutrophil Candidacidal Activity and Are Increased in the Cellular Fraction of Vaginal Samples from Women with Vulvovaginal Candidiasis

1
Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio, 41125 Emilia, Modena, Italy
2
Graduate School of Microbiology and Virology, University of Modena and Reggio, 41225 Emilia, Modena, Italy
3
Department of Medicine, University of Perugia, 06132 Perugia, Italy
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Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA
5
Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA
*
Authors to whom correspondence should be addressed.
Current Address: Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter EX4 4QD, UK.
J. Fungi 2020, 6(4), 225; https://doi.org/10.3390/jof6040225
Received: 31 July 2020 / Revised: 5 October 2020 / Accepted: 14 October 2020 / Published: 16 October 2020
(This article belongs to the Special Issue Host Defense against Fungi)
Vulvovaginal candidiasis (VVC) is primarily caused by Candida albicans and affects 75% of childbearing age women. Although C. albicans can colonize asymptomatically, disease is associated with an increased Candida burden, a loss of epithelial tolerance and a breakdown in vaginal microbiota homeostasis. VVC symptoms have been ascribed to a powerful inflammatory response associated with the infiltration of non-protective neutrophils (PMN). Here, we compared the immunological characteristics of vaginal fluids and cellular protein extracts obtained from 28 VVC women and from 23 healthy women colonized by Candida spp. We measured the levels of antibodies against fungal antigens and human autoantigens (anti-Saccharomyces cerevisiae antibodies (ASCA), C. albicans germ tube antibodies (CAGTAs) and perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)), in addition to other immunological markers. Our results show that the pANCA levels detected in the cellular protein extracts from the vaginal fluids of symptomatic women were significantly higher than those obtained from healthy colonized women. Consistent with a potential physiologically relevant role for this pANCA, we found that specific anti-myeloperoxidase antibodies could completely neutralize the ex vivo killing capacity of polymorphonuclear cells. Collectively, this preliminary study suggests for the first time that pANCA are found in the pathogenic vaginal environment and can promptly impair neutrophil function against Candida, potentially preventing a protective response. View Full-Text
Keywords: Candida; VVC; pANCA; ASCA; CAGTA Candida; VVC; pANCA; ASCA; CAGTA
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Ardizzoni, A.; Sala, A.; Colombari, B.; Giva, L.B.; Cermelli, C.; Peppoloni, S.; Vecchiarelli, A.; Roselletti, E.; Blasi, E.; Wheeler, R.T.; Pericolini, E. Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (pANCA) Impair Neutrophil Candidacidal Activity and Are Increased in the Cellular Fraction of Vaginal Samples from Women with Vulvovaginal Candidiasis. J. Fungi 2020, 6, 225.

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