Miyaji M, Nishimura K
Mycopathologia. 1983 Jun 20;82(3):129-41. doi: 10.1007/BF00439218.
We did this experiment to clarify the mechanism of granuloma formation and the killing functions of granuloma in nude mice against Blastomyces dermatitidis and Paracoccidioides brasiliensis infections. B. dermatitidis A-295 and P. brasiliensis B-1183 were the cultures used. Congenitally athymic nude (nu/nu) mice and their heterozygous (nu/+) littermates of BALB/c background were the test animals. From culture A-295, 0.1% and 1% cell suspensions (wet weight) were prepared and from culture B-1183 0.2% and 2% cells suspensions were prepared. Ten nu/+ and 10 nu/nu mice were allotted to each of four cell suspensions. For experimental blastomycosis each mouse was inoculated intravenously with 0.2 ml of the cell suspension of A-295 and for experimental paracoccidioidomycosis, with 0.15 ml of the cell suspension of B-1183. Two mice from each of the four groups were killed at 5, 8, 12, 18 and 25 days after inoculation, and histopathologic sections, stained with H&E or by PAS, were prepared from various internal organs. In the nu/nu mice inoculated with B. dermatitidis A-295 granuloma was formed in the brain tissue after the 12th day. However, mononuclear cells, which formed the granuloma, did not kill the fungal cells, and the fungal cells continued to multiply in the granuloma. On the other hand, in the heart, kidney and fat tissue, their histopathological findings after the 18th day were clumps of fungal cells with slight cell reactions. In these organs the exertion of cell-mediated immunity was necessary for granuloma formation against the fungal infection. In the nu/nu mice infected with P. brasiliensis B-1183, granuloma appeared in the brain and kidney after the 18th day and fungal cells continued to multiply within the granuloma as well as in those inoculated with culture A-295. These results show that the exertion of cell-mediated immunity plays an important role in the mouse's defense mechanisms against these fungal infections. We assume that the defense mechanisms of immunocompetent mice against B. dermatitidis or P. brasiliensis infection consist chiefly of two steps: in the first step phagocytosis by PMNs occurs and in the second step cell-mediated immunity enters into play.
我们进行这项实验是为了阐明裸鼠体内肉芽肿形成的机制以及肉芽肿对皮炎芽生菌和巴西副球孢子菌感染的杀伤功能。使用的培养物是皮炎芽生菌A - 295和巴西副球孢子菌B - 1183。实验动物是具有BALB/c背景的先天性无胸腺裸鼠（nu/nu）及其杂合子（nu/+）同窝小鼠。从培养物A - 295制备了0.1%和1%的细胞悬液（湿重），从培养物B - 1183制备了0.2%和2%的细胞悬液。将10只nu/+和10只nu/nu小鼠分配到四种细胞悬液中的每一种。对于实验性芽生菌病，每只小鼠静脉注射0.2 ml A - 295细胞悬液；对于实验性副球孢子菌病，每只小鼠静脉注射0.15 ml B - 1183细胞悬液。在接种后第5、8、12、18和25天，从四个组中的每组处死两只小鼠，并从各种内脏器官制备用苏木精和伊红（H&E）或过碘酸希夫（PAS）染色的组织病理学切片。在接种皮炎芽生菌A - 295的nu/nu小鼠中，第12天后脑组织中形成了肉芽肿。然而，形成肉芽肿 的单核细胞并未杀死真菌细胞，真菌细胞在肉芽肿中继续增殖。另一方面，在心脏、肾脏和脂肪组织中，第18天后它们的组织病理学表现是真菌细胞团伴有轻微的细胞反应。在这些器官中，针对真菌感染形成肉芽肿需要细胞介导的免疫发挥作用。在感染巴西副球孢子菌B - 1183的nu/nu小鼠中，第18天后大脑和肾脏中出现了肉芽肿，并且真菌细胞在肉芽肿内以及在接种培养物A - 295的小鼠中继续增殖。这些结果表明，细胞介导的免疫发挥在小鼠针对这些真菌感染的防御机制中起重要作用。我们推测免疫功能正常的小鼠针对皮炎芽生菌或巴西副球孢子菌感染的防御机制主要包括两个步骤：第一步是中性粒细胞进行吞噬作用，第二步是细胞介导的免疫发挥作用。
