Comparison of immune responses of yeast form and hyphae form Candida albicans to infection of vaginal epithelial cells

Abstract

Abstract:

Objective Candida albicans has morphological plasticity and can switch morphology among yeast form and hyphal form. In this study, the two different forms of Candida albicans stimulate the vaginal epithelial cells in order to compare the differences in immune response caused by them. Methods Vaginal epithelial cell lines VK2/E6E7 were treated as model. Different concentrations of activated Candida albicans and heat-inactivated Candida albicans SC5314 (MOI=10,50,100) were given to in vitro stimulate vaginal epithelial cell lines. Real-time fluorescent quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) method were used to determine the expression of proinflammatory factor TNF-α and chemokines IL-8 under different infection stage(3 h,6 h,12 h). Results Activated Candida alibcans showed hyphal form in K-SFM medium while the heat-inactivated one showed yeast form. Two infection groups showed difference in expression of IL-8 and TNF-α compared to the uninfected group significantly. Under various MOI conditions, the mRNA level of[JP+3]cytokines released by hyphal form infection group was significantly higher than that of yeast form. In especial, at the concentration of MOI=10, the protein level of cytokines released by hyphal form was higher than that of the yeast form. However, the condition turned to reversion with the increase of MOI. Conclusion Both yeast and hyphal form of Candida albicans can induce significant immune responses in vaginal epithelial cells. What's more, hyphal form can induce the immune response of vaginal epithelial cells stronger than that of yeast form under MOI=10. The difference in the immune response intensity by the two-form infection group suggested that the mechanisms of the immunity might be different between the two groups.

Key words: Candida albicans, vulvovaginal vandidiasis, hyphae, vaginal epithelium, inflammation

CLC Number:

R519.3

WANG Yu-ting, WANG Yu-zhu, LIU Jin-yan, MENG Ling-ning, LI Wei-hua, XIANG Ming-jie. Comparison of immune responses of yeast form and hyphae form Candida albicans to infection of vaginal epithelial cells[J]. Chinese Journal of Mycology, 2019, 14(4): 193-199.

References

[1] Wang FJ, Zhang D, Liu ZH, et al. Species distribution and in vitro antifungal susceptibility of vulvovaginal candida isolates in China[J]. Chin Med J (Engl), 2016, 129(10):1161-1165.
[2] Felix TC, De Brito Roder DVD, Dos Santos Pedroso R. Alternative and complementary therapies for vulvovaginal candidiasis[J]. Folia Microbiol (Praha), 2019,64(2):133-141.
[3] 徐炜新, 蔡徐山, 黄忠发, 等. 上海市嘉定区1097份真菌性阴道炎标本的病原和药物敏感性调查[J]. 诊断学理论与实践, 2017, 16(4):409-413.
[4] Sobel JD. Vulvovaginal candidosis[J]. Lancet, 2007, 369(9577):1961-1971.
[5] Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms[J]. Virulence, 2013, 4(2):119-128.
[6] Su C, Yu J, Lu Y. Hyphal development in Candida albicans from different cell states[J]. Curr Genet, 2018, 64(6):1239-1243.
[7] Pivarcsi A, Nagy I, Koreck A, et al. Microbial compounds induce the expression of pro-inflammatory cytokines, chemokines and human beta-defensin-2 in vaginal epithelial cells[J]. Microbes Infect, 2005, 7(9-10):1117-1127.
[8] Gao Y, Liang G, Wang Q, et al. Different host immunological response to C. albicans by human oral and vaginal epithelial cells[J]. Mycopathologia, 2019,184(1):1-12.
[9] Umebashi K, Tokito A, Yamamoto M, et al. Interleukin-33 induces interleukin-8 expression via JNK/c-Jun/AP-1 pathway in human umbilical vein endothelial cells[J]. PLoS One, 2018, 13(1):e0191659.
[10] Du L, Chen X, Duan Z, et al. MiR-146a negatively regulates dectin-1-induced inflammatory responses[J]. Oncotarget, 2017, 8(23):37355-37366.
[11] 胡志德, 黄元兰, 孙懿, 等. 热灭活白念珠菌对单核源性树突状细胞microRNA表达谱的影响[J]. 现代免疫学, 2013, (3):189-192.
[12] 李卫华, 刘叔文, 刘颖, 等. 脱氧胆酰酪氨酸的体外杀精和抗HIV活性研究[J]. 中华生殖与避孕杂志, 2007, 27(10):661-666.
[13] Naglik JR, Konig A, Hube B, et al. Candida albicans-epithelial interactions and induction of mucosal innate immunity[J]. Curr Opin Microbiol, 2017, 40(1):104-112.
[14] Sudbery PE. Growth of Candida albicans hyphae[J]. Nat Rev Microbiol, 2011, 9(10):737-748.
[15] De Zuani M, Paolicelli G, Zelante T, et al. Mast Cells Respond to Candida albicans infections and modulate macrophages phagocytosis of the fungus[J]. Front Immunol, 2018, 9:2829.
[16] 夏茂宁, 牛雪可, 邱文, 等. 三种不同来源白念珠菌感染对小鼠的致病性研究[J]. 贵阳医学院学报, 2018, v.43;No.211(4):6-10,21.
[17] Moyes DL, Runglall M, Murciano C, et al. A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albians in epithelial cells[J]. Cell Host Microbe, 2010, 8(3):225-235.
[18] Moyes DL, Naglik JR. Mucosal immunity and Candida albicans infection[J]. Clin Dev Immunol, 2011, 2011:346307.
[19] Gow NA, Netea MG, Munro CA, et al. Immune recognition of Candida albicans beta-glucan by dectin-1[J]. J Infect Dis, 2007, 196(10):1565-1571.
[20] Li M, Liu Z H, Chen Q, et al. Insoluble beta-glucan from the cell wall of Candida albicans induces immune responses of human THP-1 monocytes through Dectin-1[J]. Chin Med J (Engl), 2009, 122(5):496-501.
[21] Moyes DL, Murciano C, Runglall M, et al. Candida albicans yeast and hyphae are discriminated by MAPK signaling in vaginal epithelial cells[J]. PLoS One, 2011, 6(11):e26580.
[22] 李桂军, 蒋琰瑛, 周建娟, 等. 炎症因子在阴道相关炎症性疾病中的局部表达[J]. 中国中西医结合皮肤性病学杂志, 2013, 12(6):366-369.