Guimarães Júlia Garcia, de Campos Gabriela Yamazaki, Machado Michele Procópio, Oliveira Brito Patrícia Kellen Martins, Dos Reis Thaila Fernanda, Goldman Gustavo Henrique, Bonini Palma Patricia Vianna, de Campos Fraga-Silva Thais Fernanda, Cavallin Daniela Cardoso Umbelino, Venturini James, da Silva Thiago Aparecido
Department of Cellular and Molecular Biology, Ribeirao Preto Medical School, University of São Paulo, São Paulo, Brazil.
Department of Clinical Analysis, School of Pharmaceutical Sciences in Araraquara, Sao Paulo State University, São Paulo, Brazil.
Bioengineered. 2025 Dec;16(1):2458786. doi: 10.1080/21655979.2025.2458786. Epub 2025 Feb 1.
Invasive fungal infections (IFIs) are responsible for elevated rates of morbidity and mortality, causing around of 1.5 million deaths annually worldwide. One of the main causative agents of IFIs is , and non-albicans species have emerged as a spreading global public health concernment. Furthermore, COVID-19 has contributed to a boost in the incidence of IFIs, such as mucormycosis, in which is the most prevalent causative agent. The effector host immune response against IFIs depends on the activity of T cells, which are susceptible to the regulatory effects triggered by fungal virulence factors. The fungal cell wall plays a crucial role as a virulence factor, and its remodeling compromises the development of a specific T-cell response. The redirection of Jurkat T cells to target spp. by recognizing targets expressed on the fungal cell wall can be facilitated using chimeric antigen receptor (CAR) technology. This study generated an M-CAR that contains an scFv with specificity to α-1,6 mannose backbone of fungal mannan, and the expression of M-CAR on the surface of modified Jurkat cells triggered a strong activation against (hyphae form), (hyphae form), (pseudohyphal form), and (yeast form). Moreover, M-CAR Jurkat cells recognized spores, which induced high expression of cell activation markers. Thus, a novel Mannan-specific CAR enabled strong signal transduction in modified Jurkat cells in the presence of spp. or .
侵袭性真菌感染(IFI)是导致发病率和死亡率上升的原因,在全球范围内每年造成约150万人死亡。IFI的主要致病因素之一是[未提及具体真菌名称],而非白色念珠菌属已成为一个日益严重的全球公共卫生问题。此外,COVID-19导致IFI发病率上升,如毛霉病,其中[未提及具体真菌名称]是最常见的致病因素。宿主针对IFI的效应免疫反应取决于T细胞的活性,而T细胞易受真菌毒力因子触发的调节作用影响。真菌细胞壁作为一种毒力因子起着关键作用,其重塑会损害特异性T细胞反应的发展。利用嵌合抗原受体(CAR)技术可以促进Jurkat T细胞通过识别真菌细胞壁上表达的靶标来靶向[未提及具体真菌名称]属。本研究构建了一种M-CAR,其包含对真菌甘露聚糖的α-1,6甘露糖主链具有特异性的单链抗体片段(scFv),M-CAR在修饰的Jurkat细胞表面的表达引发了对[未提及具体真菌名称](菌丝体形式)、[未提及具体真菌名称](菌丝体形式)、[未提及具体真菌名称](假菌丝体形式)和[未提及具体真菌名称](酵母形式)的强烈激活。此外,M-CAR Jurkat细胞识别[未提及具体真菌名称]孢子,这诱导了细胞激活标志物的高表达。因此,一种新型的甘露聚糖特异性CAR在存在[未提及具体真菌名称]属或[未提及具体真菌名称]的情况下能够在修饰的Jurkat细胞中实现强信号转导。