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.
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