Alcohol dehydrogenase of Candida albicans triggers differentiation of THP-1 cells into macrophages

• Main Authors: Yanglan Liu, Yuxue Ou, Luping Sun, Wenqing Li, Jinghong Yang, Xiaohuan Zhang, Yan Hu
• Format: Article
• Language: English
• Published: Elsevier 2019-07-01
• Series: Journal of Advanced Research
• Online Access: http://www.sciencedirect.com/science/article/pii/S2090123219300347

Candida albicans proteins located on the cell wall and in the cytoplasm have gained great attention because they are not only involved in cellular metabolism and the maintenance of integrity but also interact with host immune systems. Previous research has reported that enolase from C. albicans exhibits high immunogenicity and effectively protects mice against disseminated candidiasis. In this study, alcohol dehydrogenase (ADH) of C. albicans was cloned and purified for the first time, and this study focused on evaluating its effects on the differentiation of the human monocytic cell line THP-1. The morphological features of THP-1 cells exposed to ADH were similar to those of phorbol-12-myristate acetate-differentiated (PMA-differentiated) macrophages. Functionally, ADH enhanced the adhesion, phagocytosis, and killing capacities of THP-1 cells. A flow cytometric assay demonstrated that ADH-induced THP-1 cells significantly increased CD86 and CD11b expression. The production of IL-1β, IL-6, and TNF-α by cells increased in the presence of ADH. As expected, after pretreatment with a MEK inhibitor (U0126), ADH-induced THP-1 cells exhibited unaltered morphological features, eliminated ERK1/2 phosphorylation, prevented CD86/CD11b upregulation and inhibited pro-inflammatory cytokine increase. Collectively, these results suggest that ADH enables THP-1 cells to differentiate into macrophages via the ERK pathway, and it may play an important role in the immune response against fungal invasion. Keywords: Alcohol dehydrogenase, Moonlighting proteins, Candida albicans, THP-1 cells, Macrophage differentiation, ERK pathway