Arancia G, Molinari A, Crateri P, Stringaro A, Ramoni C, Dupuis M L, Gomez M J, Torosantucci A, Cassone A
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
Infect Immun. 1995 Jan;63(1):280-8. doi: 10.1128/iai.63.1.280-288.1995.
During incubation in vitro with yeast or germ tube forms of Candida albicans, only 2 to 6% of freshly isolated human natural killer (NK) cells (> 85% CD16+, CD56+, CD3-; < 15% CD3+; cytolytic for the NK-susceptible target K562 but not for the NK-resistant target DAUDI), were seen to interact with the fungal cells. As seen under the electron microscope, the contact area had a limited extent and was narrow, and neither the surface nor the intracytoplasmic organization of the NK cell was altered. In contrast, more than 30% of interleukin-2-activated NK (LAK) cells (> 96% CD16+, CD56+, CD3-; 1.5% CD3+; cytolytic for both K562 and DAUDI targets) interacted closely with the fungus. This interaction was particularly extensive with the surface of the fungal germ tube that was intimately enveloped by villous protrusions from the lymphocyte surface. The fungus-interacting LAK cell also showed a remarkable redistribution of surface microvilli and polarization of cytoplasmic organelles, such as the Golgi apparatus, centrioles, and granules, toward the area of fungal contact. Together with the elevated cytolytic potential against the K562 and DAUDI targets, all the morphological data suggested the presence of a potentially active lytic machinery in the fungus-interacting LAK cell. Nonetheless, two independent assays for anticandidal activity did not show consistent killing or fungal growth inhibition by either fresh NK or LAK cells. While offering direct evidence of the strong interaction between human LAK cells and the germ tubes, precursors of tissue-invasive hyphal forms of C. albicans, our observations also suggest that this interaction may not be sufficient to kill the fungus or arrest its growth.
在与白色念珠菌的酵母或芽管形式进行体外孵育期间,仅2%至6%的新鲜分离的人类自然杀伤(NK)细胞(>85% CD16+、CD56+、CD3-;<15% CD3+;对NK敏感靶标K562具有细胞毒性,但对NK抗性靶标DAUDI无细胞毒性)与真菌细胞相互作用。在电子显微镜下观察到,接触区域范围有限且狭窄,NK细胞的表面和胞质内结构均未改变。相比之下,超过30%的白细胞介素-2激活的NK(LAK)细胞(>96% CD16+、CD56+、CD3-;1.5% CD3+;对K562和DAUDI靶标均具有细胞毒性)与真菌紧密相互作用。这种相互作用在真菌芽管表面尤为广泛,芽管被淋巴细胞表面的绒毛状突起紧密包裹。与真菌相互作用的LAK细胞还表现出表面微绒毛的显著重新分布以及细胞质细胞器,如高尔基体、中心粒和颗粒,向真菌接触区域的极化。连同对K562和DAUDI靶标的细胞毒性潜力升高,所有形态学数据表明在与真菌相互作用的LAK细胞中存在潜在活跃的裂解机制。尽管如此,两种独立的抗念珠菌活性测定均未显示新鲜NK或LAK细胞对念珠菌有一致的杀伤或真菌生长抑制作用。我们的观察结果虽然提供了人类LAK细胞与组织侵袭性白色念珠菌菌丝形式的前体芽管之间强烈相互作用的直接证据,但也表明这种相互作用可能不足以杀死真菌或阻止其生长。