The morphological switch between yeast and hyphae of Candida albicans is essential for its interaction with the host defense system. However, the lack of understanding of host–pathogen interactions during C. albicans infection greatly hampers the development of effective immunotherapies. Here, we found that priming with the C. albicans FLO8-deficient (flo8) mutant, locked in yeast form, protected mice from subsequent lethal C. albicans infection. Deficiency of Dectin-2, a fungus-derived α-mannan recognition receptor, completely blocked flo8 mutant-induced protection. Mechanistically, the flo8 mutant-induced Dectin-2/CARD9-mediated IL-10 production in DCs and macrophages to block thymus atrophy by inhibiting the C. albicans-induced apoptosis of thymic T cells, which facilitated the continuous output of naive T cells from the thymus to the spleen. Continuous recruitment of naive T cells to the spleen enhanced Th1-biased antifungal immune responses. Consequently, depletion of CD4+ T cells or blockade of IL-10 receptor function using specific antibodies in mice completely blocked the protective effects of flo8 mutant priming against C. albicans infection. Moreover, mannans exposed on the surface of the flo8 mutant were responsible for eliciting protective immunity by inhibiting the C. albicans-induced apoptosis of thymic T cells to sustain the number of naive T cells in the spleen. Importantly, priming with the flo8 mutant extensively protected mice from polymicrobial infection caused by cecal ligation and puncture (CLP) by enhancing Th1-biased immune responses. Together, our findings imply that targeting FLO8 in C. albicans elicits protective immune responses against polymicrobial infections and that mannans extracted from the flo8 mutant are potential immunotherapeutic candidate(s) for controlling infectious diseases.

白色念珠菌的酵母和菌丝之间的形态转换对于其与宿主防御系统的相互作用至关重要。然而，缺乏对白色念珠菌感染期间宿主与病原体相互作用的了解极大地阻碍了有效免疫疗法的发展。在这里，我们发现用锁定在酵母形式的白色念珠菌 FLO8缺陷 ( flo8 ) 突变体进行引发，可以保护小鼠免受随后致命的白色念珠菌感染。 Dectin-2（一种真菌来源的 α-甘露聚糖识别受体）的缺陷完全阻断了flo8突变体诱导的保护。从机制上讲， flo8突变体诱导Dectin-2/CARD9介导的DC和巨噬细胞产生IL-10，通过抑制白色念珠菌诱导的胸腺T细胞凋亡来阻止胸腺萎缩，从而促进初始T细胞的持续输出。胸腺到脾脏。持续向脾脏募集初始 T 细胞可增强 Th1 型抗真菌免疫反应。因此，在小鼠中使用特异性抗体消除 CD4+ T 细胞或阻断 IL-10 受体功能，完全阻断了flo8突变体引发对白色念珠菌感染的保护作用。此外，暴露在flo8突变体表面的甘露聚糖通过抑制白色念珠菌诱导的胸腺T细胞凋亡来维持脾脏中幼稚T细胞的数量，从而引发保护性免疫。重要的是，通过增强 Th1 偏向的免疫反应，用flo8突变体启动可广泛保护小鼠免受盲肠结扎穿刺 (CLP) 引起的多种微生物感染。 总之，我们的研究结果表明，针对白色念珠菌中的FLO8会引发针对多种微生物感染的保护性免疫反应，并且从flo8突变体中提取的甘露聚糖是控制传染病的潜在免疫治疗候选者。