Ying Gao1, Guanzhao Liang1, Qiong Wang1, Xiaodong She1, Dongmei Shi1,2, Yongnian Shen1, Xiaohong Su3, Xiang Wang4, Wenmei Wang4, Dongmei Li1,5, Weida Liu6. 1. Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Jiangsu Key Laboratory of Molecular Biology for Skin Disease and STIs, Nanjing, 210042, Jiangsu, China. 2. Department of Dermatology, Jining No.1 People's Hospital, Jining, 272001, Shandong, China. 3. STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Nanjing, 210042, Jiangsu, China. 4. Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 210008, Jiangsu, China. 5. Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, 20057, USA. 6. Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Jiangsu Key Laboratory of Molecular Biology for Skin Disease and STIs, Nanjing, 210042, Jiangsu, China. liumyco@hotmail.com.
Abstract
OBJECTIVE: The immunological mechanisms behind different mucosa against candidiasis are largely unknown. In this study, we investigate the natural protective mechanisms and local cytokine responses of C. albicans-infected oral and vaginal epithelial cells. METHOD: The cell lines (Leuk-1 and VK2/E6E7) were cultured with C. albicans (SC5314, Δals3, and Δssa1) in indicated ratio, respectively. The morphological changes and colony growth of C. albicans were observed to evaluate the fungicidal ability of epithelial cells, and the cellular morphological changes and LDH activity measurements were used to assess cell damage. Further, we assess the production of cytokines and chemokines in co-culture supernatants using enzyme-linked immunosorbent assay (ELISA). RESULT: Our results show that the oral and vaginal epithelial cells use different strategies to combat this pathogen. Infected oral epithelial cells are adept at the production of cytokines (GM-CSF, IL-1α, and IL-1β) and chemokines (IL-8, MIP-3α, and RANTES), and yet, vaginal cells are more proficient at direct fungal killing. However, both epithelial cells play only a minor role in adaptive immunity to C. albicans. Further, C. albicans Als3p and Ssa1p genes also participate in local immune response since deletion of ALS3 or SSA1 causes reduction in cytokine and chemokine levels in both oral and vaginal cells. The dramatic decreases in both fungal % of cytotoxicity and the secretion of such cytokines as GM-CSF, MIP-3α, and RANTES in Δssa1-infected oral cells were consistent with a delayed germination process in that mutant. CONCLUSION: Human oral and vaginal epithelial cells performed different host response to C. albicans by fungal killing ability or secreting cytokines and chemokines.
OBJECTIVE: The immunological mechanisms behind different mucosa against candidiasis are largely unknown. In this study, we investigate the natural protective mechanisms and local cytokine responses of C. albicans-infected oral and vaginal epithelial cells. METHOD: The cell lines (Leuk-1 and VK2/E6E7) were cultured with C. albicans (SC5314, Δals3, and Δssa1) in indicated ratio, respectively. The morphological changes and colony growth of C. albicans were observed to evaluate the fungicidal ability of epithelial cells, and the cellular morphological changes and LDH activity measurements were used to assess cell damage. Further, we assess the production of cytokines and chemokines in co-culture supernatants using enzyme-linked immunosorbent assay (ELISA). RESULT: Our results show that the oral and vaginal epithelial cells use different strategies to combat this pathogen. Infected oral epithelial cells are adept at the production of cytokines (GM-CSF, IL-1α, and IL-1β) and chemokines (IL-8, MIP-3α, and RANTES), and yet, vaginal cells are more proficient at direct fungal killing. However, both epithelial cells play only a minor role in adaptive immunity to C. albicans. Further, C. albicans Als3p and Ssa1p genes also participate in local immune response since deletion of ALS3 or SSA1 causes reduction in cytokine and chemokine levels in both oral and vaginal cells. The dramatic decreases in both fungal % of cytotoxicity and the secretion of such cytokines as GM-CSF, MIP-3α, and RANTES in Δssa1-infected oral cells were consistent with a delayed germination process in that mutant. CONCLUSION:Human oral and vaginal epithelial cells performed different host response to C. albicans by fungal killing ability or secreting cytokines and chemokines.