阴道上皮细胞源性IgG抗白假丝酵母菌免疫应答机制及Farnesol、雌激素、乳杆菌对其免疫功能干预的研究

The etiology and pathogenesis of vulvovaginal candidiasis（VVC） is complicatedly recurrent or refractory, and the common anti-fungal drugs always result in insufficient treatment, which can lead to the occurrence of this disease and drug resistance. Vaginal epithelial cells (VEC) are the main natural barrier against Candida albicans in vivo. Recently, one of our unpublished study has found that vaginal epithelial cells can secrete a kind of non-B cell derived Immunoglobulin G (IgG). Based on the previous study, we plan to test whether normal human vaginal tissue can secrete non-B cell derived IgG by using the immunohistochemical staining, to adopt by siRNA interference technology to knockdown the expression of IgG and iTRAQ quantitative proteomics technology comprehensively exploring the key role of non-B cell derived IgG against Candida albicans; to discuss the effect of quorum sensing molecule Farnesol, Estrogen and Lactobacillus on the local immune function of VEC against Candida infection, to further understand the drug development value of Farnesol. What’s more, we also plan to use the rat model to study the effects of the above factors on the local immune function of the vagina, revealing the pathogenesis of VVC from the view point of immunology, to block fungal carriers developing symptomatic infector，and to provide a theoretical basis for developing new methods of prevention and control.

外阴阴道假丝酵母菌病（VVC）的病因及发病机制比较复杂且顽固复发，目前常用的抗真菌药物又易产生治疗不彻底从而导致病情反复和耐药性的发生。阴道上皮细胞（VEC）既是假丝酵母菌侵袭的主要靶细胞，还是对抗假丝酵母菌的主要天然屏障。最近，我们一项未发表的研究发现，阴道上皮细胞能够分泌一种IgG类抗体。本项目在前期研究基础上，拟采用免疫组化染色检验正常人阴道组织是否能分泌这种IgG,采用siRNA干扰技术敲除IgG的表达，iTRAQ定量蛋白质组学方法技术全面研究该IgG的功能；探讨真菌信号分子Farnesol、雌激素及乳杆菌对VEC抗假丝酵母菌局部免疫的影响，进一步了解Farnesol的作用活性及开发价值。此外，我们还拟采用大鼠动物模型来探讨上述多种因素对阴道局部免疫功能的影响从免疫学的角度揭示VVC的发病机制，从而阻断假丝酵母菌携带者发展为有症状感染者，为从微生态方面开发新的防治方法提供新思路。

阴道上皮细胞既是假丝酵母菌侵袭的主要靶细胞，还是对抗假丝酵母菌的主要天然屏障。已成功采用免疫组化染色证实正常人阴道组织能分泌非B细胞来源的IgG,采用siRNA干扰技术敲除IgG的表达，iTRAQ定量蛋白质组学方法技术全面研究该IgG的功能，证实该IgG可能发挥天然抗体的作用；探讨真菌信号分子Farnesol、雌激素及乳杆菌对阴道上皮细胞抗假丝酵母菌局部免疫的影响，进一步了解Farnesol的作用活性及开发价值。成功构建大鼠外阴阴道假丝酵母菌病模型，并采用动物模型来探讨上述多种因素对阴道局部免疫功能的影响从免疫学的角度揭示外阴阴道假丝酵母菌病的发病机制。