Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
Section of Dentistry for the Disabled, Department of Oral Growth and Development, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
FEMS Yeast Res. 2018 May 1;18(3). doi: 10.1093/femsyr/foy018.
Candida albicans is a human commensal that causes opportunistic infections. Th17 cells provide resistance against mucosal infection with C. albicans; however, the T cell antigens remain little known. Our final goal is to find effective T cell antigens of C. albicans that are responsible for immunotherapy against candidiasis. Here, we prepared fractions including cytosol, membrane and cell wall from yeast and mycelial cells. Proteins derived from a membrane fraction of mycelial cells effectively induced differentiation of CD4+ T cells into IL-17A-producing Th17 cells. To confirm the immunological response in vivo of proteins from mycelial membrane, we performed adoptive transfer experiments using ex vivo stimulated CD4+ T cells from IL-17A-GFP reporter mice. Mycelial membrane-differentiated CD4+ Th17 cells adoptively transferred intravenously prevented oral candidiasis by oral infection of C. albicans, compared with control anti-CD3-stimulated CD4+ T cells. This was confirmed by the clinical score and the number of neutrophils on the infected tissues. These data suggest that effective T cell antigens against candidiasis could be present in the membrane protein fraction of mycelial cells. The design of novel vaccination strategies against candidiasis will be our next step.
白色念珠菌是一种人体共生菌,可引起机会性感染。Th17 细胞提供了针对白色念珠菌黏膜感染的抵抗力;然而,T 细胞抗原仍然知之甚少。我们的最终目标是找到负责抗念珠菌免疫治疗的白色念珠菌有效 T 细胞抗原。在这里,我们从酵母和菌丝细胞中制备了包括胞质溶胶、膜和细胞壁在内的馏分。来自菌丝细胞膜部分的蛋白质有效地诱导 CD4+T 细胞分化为产生 IL-17A 的 Th17 细胞。为了确认菌丝膜蛋白在体内的免疫反应,我们使用 IL-17A-GFP 报告小鼠的体外刺激 CD4+T 细胞进行了过继转移实验。与对照抗 CD3 刺激的 CD4+T 细胞相比,静脉内过继转移菌丝膜分化的 CD4+Th17 细胞可通过白色念珠菌的口腔感染预防口腔念珠菌病,这一点通过临床评分和受感染组织上的中性粒细胞数量得到证实。这些数据表明,针对念珠菌病的有效 T 细胞抗原可能存在于菌丝细胞的膜蛋白部分。设计针对念珠菌病的新型疫苗接种策略将是我们的下一步。