Encephalitozoon cuniculi is a fungi-related, obligate, zoonotic, spore-forming intracellular eukaryotic microorganism. This emerging pathogen causes granulomas to form in the brain and kidneys of infected individuals. The objective of the current study was to detect the distribution of TNF-α- and IL-4-positive cells using immunohistochemistry within these granulomas in both infected immunocompetent (group A) and immunosuppressed (group B) New Zealand white rabbits. In the brain, labeled TNF-α immune cells were mainly located in the granuloma peripheries in group B. Granulomas examined in the kidneys of groups A and B were TNF-α positive, but were significantly different (p < 0.001) when compared with the brain. IL-4-producing immune cells in the brain and kidneys were disseminated within granulomas in groups A and B; however, no significant difference (p > 0.05), was observed. IL-4 positive cells were more numerous in brain sections of group B and differed significantly (p < 0.05) when compared with kidneys. Granulomas were not observed in control animals (groups C and D). In conclusion, we identified TNF-α positive cells in both the brain and kidneys of immunocompetent and immunosuppressed animals; IL-4 positive cells were numerous in the brains of immunosuppressed rabbits; however, in terms of percentage were numerous in the brains of immunocompetent rabbits. Immunosuppression appeared to stimulate a change in the cellular phenotype of Th1- to Th2-like granulomas in the brain and kidneys via an unknown mechanism. Expression of pro- and pre-inflammatory cytokines in microsporidian granulomas suggests a mechanism by which E. cuniculi evades the immune response, causing more severe disease. These results increase our understanding of TNF-α and IL-4-positive cells within the E. cuniculi granuloma microenvironment.

中文翻译：

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感染兔脑炎原虫的免疫功能正常和免疫抑制的新西兰白兔肉芽肿中 TNF-α 和 IL-4 的免疫组织化学定位


兔脑炎孢子虫是一种与真菌相关的、专性的、人畜共患的、形成孢子的细胞内真核微生物。这种新出现的病原体会导致感染者的大脑和肾脏形成肉芽肿。本研究的目的是使用免疫组织化学方法检测感染的免疫功能正常（A 组）和免疫抑制（B 组）新西兰白兔的肉芽肿内 TNF-α 和 IL-4 阳性细胞的分布。 B组脑内标记的TNF-α免疫细胞主要位于肉芽肿周围。A组和B组肾脏肉芽肿均为TNF-α阳性，但与对照组相比差异显着（p < 0.001）。脑。 A 组和 B 组的大脑和肾脏中产生 IL-4 的免疫细胞散布在肉芽肿内；然而，没有观察到显着差异（p > 0.05）。 B 组脑切片中 IL-4 阳性细胞数量较多，且与肾脏相比差异显着 (p < 0.05)。在对照动物（C 组和 D 组）中未观察到肉芽肿。总之，我们在免疫功能正常和免疫抑制的动物的大脑和肾脏中发现了 TNF-α 阳性细胞；免疫抑制兔子的大脑中存在大量IL-4阳性细胞；然而，就百分比而言，在免疫功能正常的兔子的大脑中，这一比例很高。免疫抑制似乎通过一种未知的机制刺激大脑和肾脏中 Th1 样肉芽肿向 Th2 样肉芽肿的细胞表型的变化。微孢子虫肉芽肿中促炎细胞因子和前炎细胞因子的表达提示了兔小孢子虫逃避免疫反应、导致更严重疾病的机制。 这些结果增加了我们对 E. cuniculi 肉芽肿微环境中 TNF-α 和 IL-4 阳性细胞的了解。