Mnn10 Maintains Pathogenicity in Candida albicans by Extending α-1,6-Mannose Backbone to Evade Host Dectin-1 Mediated Antifungal Immunity

• DOI: 10.1371/journal.ppat.1005617
• Publication Date: 2016-05-04T18:07:53Z
• Authors: Shi Qun Zhang; Zui Zou; Hui Shen; Shuai Shuai Shen; Qi Miao; Xin Huang; Wei Liu; Li Ping Li; Si Min Chen; Lan Yan; Jun Dong Zhang; Jing Jun Zhao; Guo Tong Xu; Mao Mao An; Yuan Ying Jiang
• Keywords: Mannan

The cell wall is a dynamic structure that important for the pathogenicity of Candida albicans. Mannan, which located in outermost layer wall, has been shown to contribute pathogenesis C. albicans, however, molecular mechanism by this occurs remains unclear. Here we identified novel α-1,6-mannosyltransferase encoded MNN10 We found Mnn10 required α-1,6-mannose backbone biosynthesis and polysaccharides organization. Deletion resulted significant attenuation albicans murine systemic candidiasis model. Inhibition extension did not, impact invasive ability vitro. Notably, mnn10 mutant restored capacity athymic nude mice, further supports notion an enhanced host antifungal defense related change. induced Th1 Th17 mediated immunity, recruitment neutrophils monocytes pathogen clearance vivo. also demonstrated could unmask surface β-(1,3)-glucan, crucial pathogen-associated pattern (PAMP) recognized Dectin-1. Our results demonstrate stimulate Dectin-1 dependent immune response macrophages vitro, including activation nuclear factor-κB, mitogen-activated protein kinase pathways, secretion specific cytokines such as TNF-α, IL-6, IL-1β IL-12p40. In summary, our study indicated critical via shielding β-glucan from recognition recognition. Moreover, work suggests inhibition may represent modality reduce