Barluzzi R, Mazzolla R, Brozzetti A, Puliti M, Mariucci G, Mosci P, Bistoni F, Blasi E
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
J Neuroimmunol. 1997 Oct;79(1):37-48. doi: 10.1016/s0165-5728(97)00105-7.
Here we studied the involvement of PCA-2, a low-virulent strain of Candida albicans known to act as a potent stimulating agent in the development of cryptococcal meningoencephalitis. To this purpose, mice received saline or PCA-2 intracerebrally 7 days before lethal local challenge with Cryptococcus neoformans. We found that, following C. neoformans challenge, PCA-2-treated but not saline-treated mice exhibited (a) delayed brain colonization, (b) enhanced median survival times, (c) massive local immune reaction consisting of abundant astrocytes, microglial and inflammatory cells, and (d) a peculiar trend of cytokine gene expression, including high steady-state levels of interleukin (IL)-1 beta and tumor necrosis factor alpha transcripts, fluctuating levels of interferon gamma and inducible nitric oxide synthase mRNA and lately detectable IL-6 gene expression. PCA-2-mediated immunostimulating properties were partially impaired by aminoguanidine or pentoxifylline treatment, further strengthening the conclusion that soluble mediators, including proinflammatory cytokines and nitric oxide, are important defense elements against cryptococcal meningoencephalitis.
在此，我们研究了白色念珠菌低毒力菌株PCA - 2的作用，已知该菌株在新型隐球菌性脑膜脑炎的发展过程中可作为一种强效刺激剂。为此，在对小鼠进行致死性局部新型隐球菌攻击前7天，给小鼠脑内注射生理盐水或PCA - 2。我们发现，在新型隐球菌攻击后，接受PCA - 2处理而非生理盐水处理的小鼠表现出：(a) 脑内定植延迟；(b) 中位生存时间延长；(c) 由大量星形胶质细胞、小胶质细胞和炎性细胞组成的局部免疫反应增强；(d) 细胞因子基因表达的特殊趋势，包括白细胞介素(IL)-1β和肿瘤坏死因子α转录本的高稳态水平、干扰素γ和诱导型一氧化氮合酶mRNA水平波动以及较晚可检测到的IL - 6基因表达。氨基胍或己酮可可碱处理会部分损害PCA - 2介导的免疫刺激特性，这进一步强化了如下结论：包括促炎细胞因子和一氧化氮在内的可溶性介质是抵御新型隐球菌性脑膜脑炎的重要防御要素。
