Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein
Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein
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DOI：
10.1126/scitranslmed.adi3363
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发表时间：
2023-12-06
影响因子：
17.1
通讯作者：
Wilson，Duncan
中科院分区：
文献类型：
--
作者：
Roselletti，Elena;Pericolini，Eva;Wilson，Duncan
据估计，每年有5亿例外阴阴道念珠菌病（VVC）。VVC最常见由白色念珠菌引起，在这种情况下，其触发非保护性中性粒细胞浸润、侵袭性局部炎症和症状性疾病。尽管它的流行，很少有人知道的分子机制支撑这种真菌感染的免疫病理学。在这项研究中，我们描述了VVC免疫病理学的分子决定因素和一种潜在的直接预防疾病的方法。为了应对锌的限制，C。白色念珠菌释放一种微量矿物质结合分子，称为Pra1（pH调节抗原）。在这里，我们发现，在阴道感染过程中，PRA1基因表达强烈上调，其表达与女性促炎细胞因子浓度呈正相关。PRA1基因的缺失可以预防小鼠的阴道炎症，锌溶液的应用可以下调该基因的表达，也可以阻断免疫病理学。我们还表明，用锌凝胶治疗复发性VVC的妇女可预防再感染。因此，我们已经确定了症状性VVC的关键介质，使我们有机会制定一系列预防措施来对抗这种疾病。
Candidacauses an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused byCandida albicans, which, in this setting, triggers nonprotective neutrophil infiltration, aggressive local inflammation, and symptomatic disease. Despite its prevalence, little is known about the molecular mechanisms underpinning the immunopathology of this fungal infection. In this study, we describe the molecular determinant of VVC immunopathology and a potentially straightforward way to prevent disease. In response to zinc limitation,C. albicansreleases a trace mineral binding molecule called Pra1 (pH-regulated antigen). Here, we show that thePRA1gene is strongly up-regulated during vaginal infections and that its expression positively correlated with proinflammatory cytokine concentrations in women. Genetic deletion ofPRA1prevented vaginal inflammation in mice, and application of a zinc solution down-regulated expression of the gene and also blocked immunopathology. We also show that treatment of women suffering from recurrent VVC with a zinc gel prevented reinfections. We have therefore identified a key mediator of symptomatic VVC, giving us an opportunity to develop a range of preventative measures for combatting this disease.