BIOMOLECULAR EVENTS INVOLVED IN ANTICRYPTOCOCCAL RESISTANCE IN THE BRAIN

We have recently shown that intracerebral (i.c.) administration of hea t-killed Cryptococcus neoformans (HCN) enhances mouse resistance to a subsequent local challenge with lethal doses of viable yeast cells. He re we show that i.c. administration of HCN is also effective in signif icantly delaying brain colonization of mice intravenously infected wit h viable C. neoformans. PCR analysis revealed that interleukin 6 (IL-6 ) and IL-1 beta gene expression occurs in brains of HCN-treated mice b ut not in brains of saline-treated controls. In contrast, no differenc es are observed in terms of tumor necrosis factor alpha and IL-1 alpha gene transcripts, which are slightly and highly detectable, respectiv ely, in saline-treated mice and which remain such also following HCN t reatment. Furthermore, i.c. administration of exogenous IL-6 or IL-1 b eta, but not tumor necrosis factor alpha, before local challenge with viable C. neoformans results in significantly reduced microbial counts in the brain and blood and in increased mouse survival, Taken togethe r, these observations provide initial evidence that brain anticryptoco ccal resistance involves elicitation of a local cytokine response, inv olving primarily IL-6 and IL-1 beta.