Faculty of Graduate Studies, Mahidol University, Nakhon Pathom, Thailand.
Siriraj Integrative Center for Neglected Parasitic Diseases, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, 7th floor Adulyadejvikrom Building, 2 Wang Lang Road, Khwaeng Siriraj, Khet Bangkok-noi, Bangkok, 10700, Thailand.
Parasit Vectors. 2022 Jun 27;15(1):232. doi: 10.1186/s13071-022-05306-7.
Environmental protozoa need an adaptation mechanism to survive drastic changes in niches in the human body. In the brain parenchyma, Balamuthia mandrillaris trophozoites, which are causative agents of fatal brain damage, must acquire nutrients through the ingestion of surrounding cells. However, the mechanism deployed by the trophozoites for cellular uptake remains unknown.
Amoebic ingestion of human neural cell components was investigated using a coculture system of clinically isolated B. mandrillaris trophozoites and human neuroblastoma SH-SY5Y cells. Cell-to-cell interactions were visualized in a three-dimensional manner using confocal and holotomographic microscopes.
The B. mandrillaris trophozoites first attached themselves to human neuroblastoma SH-SY5Y cells and then twisted themselves around the cytoplasmic bridge. Based on fluorescence-based cell tracking, the B. mandrillaris trophozoites then inserted invadopodia into the cytoplasm of the human cells. Subsequently, the human protein-enriched components were internalized into the trophozoites in the form of nonmembranous granules, whereas the human lipids were dispersed in the cytoplasm. Intervention of trogocytosis, a process involving nibbling on parts of the target cells, failed to inhibit this cellular uptake.
Human cell ingestion by B. mandrillaris trophozoites likely differs from trogocytosis, suggesting that a pathogen-specific strategy can be used to ameliorate brain damage.
环境原生动物需要一种适应机制来在人体内部小生境的剧烈变化中生存。在脑实质中,引起致命性脑损伤的曼氏巴尔通体滋养体必须通过摄取周围细胞来获取营养。然而,滋养体用于细胞摄取的机制尚不清楚。
使用临床分离的巴尔通体滋养体和人神经母细胞瘤 SH-SY5Y 细胞的共培养系统,研究了滋养体对人神经细胞成分的吞噬作用。使用共聚焦和全断层显微镜以三维方式可视化细胞间相互作用。
巴尔通体滋养体首先附着在人神经母细胞瘤 SH-SY5Y 细胞上,然后在细胞质桥周围扭曲自身。基于荧光标记的细胞追踪,巴尔通体滋养体随后将入侵伪足插入人细胞的细胞质中。随后,富含人类蛋白质的成分以非膜性颗粒的形式被内化到滋养体中,而人类脂质则分散在细胞质中。吞噬作用的干预,即吞噬部分靶细胞的过程,未能抑制这种细胞摄取。
巴尔通体滋养体吞噬人细胞的过程可能与吞噬作用不同,这表明可以采用病原体特异性策略来减轻脑损伤。