A LOW VIRULENT-STRAIN OF CANDIDA-ALBICANS ENHANCES BRAIN ANTICRYPTOCOCCAL DEFENSES - CHARACTERIZATION OF THE LOCAL IMMUNE-REACTION BY RT-PCR AND HISTOCHEMICAL ANALYSIS

Here we studied the involvement of PCA-2, a low-virulent strain of Can dida albicans known to act as a potent stimulating agent in the develo pment of cryptococcal meningoencephalitis. To this purpose, mice recei ved saline or PCA-2 intracerebrally 7 days before lethal local challen ge with Cryptococcus neoformans. We found that, following C, neoforman s challenge, PCA-2-treated but not saline-treated mice exhibited (a) d elayed brain colonization, (b) enhanced median survival times, (c) mas sive local immune reaction consisting of abundant astrocytes, microgli al and inflammatory cells, and (d) a peculiar trend of cytokine gene e xpression, including high steady-state levels of interleukin (IL)-1 be ta and tumor necrosis factor alpha transcripts, fluctuating levels of interferon gamma and inducible nitric oxide synthase mRNA and lately d etectable IL-6 gene expression, PCA-2-mediated immunostimulating prope rties were partially impaired by aminoguanidine or pentoxifylline trea tment, further strengthening the conclusion that soluble mediators, in cluding proinflammatory cytokines and nitric oxide, are important defe nse elements against cryptococcal meningoencephalitis. (C) 1997 Elsevi er Science B.V.