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白念珠菌菌丝膜诱导分化的 Th17 细胞预防口腔念珠菌病。

Th17 cells differentiated with mycelial membranes of Candida albicans prevent oral candidiasis.

机构信息

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.

出版信息

FEMS Yeast Res. 2018 May 1;18(3). doi: 10.1093/femsyr/foy018.

DOI:10.1093/femsyr/foy018
PMID:29462298
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6019029/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/535c194cc132/foy018fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/f6884f6fa87b/foy018fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/9246fe57861e/foy018fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/2e5549ed1df3/foy018fig3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/0773841f70b9/foy018fig3b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/535c194cc132/foy018fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/f6884f6fa87b/foy018fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/9246fe57861e/foy018fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/2e5549ed1df3/foy018fig3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/0773841f70b9/foy018fig3b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5282/6019029/535c194cc132/foy018fig4.jpg

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