BIOMOLECULAR EVENTS INVOLVED IN THE ESTABLISHMENT OF BRAIN ANTICANDIDAL RESISTANCE

Using a murine model, we have demonstrated the establishment of cerebr al resistance to local lethal challenge with Candida albicans strain C A-6, by previous intracerebral (i.c.) infection with the low-virulent strain PCA-2. Here we show that i.c. infection with PCA-2 is effective in drastically reducing brain colonization following secondary infect ion with CA-6. As assessed by colony forming unit assay and histopatho logical analysis, microbial counts are impaired, granuloma formation a nd hyphal growth are also reduced in brains of PCA-2- and CA-B-infecte d mice with respect to CA-6-challenged mice. Furthermore, using PCR st udies, we found that, while PCA-2 (i.e. healing infection) induces tra nsient cytokine gene expression in the mouse brain, CA-6 lethal challe nge results in long-lasting (until mouse death) high levels of all cyt okine gene transcripts assessed. Finally, brains from mice that will r esist CA-6 challenge, because of previous infection with PCA-2, also e xhibit a transient induction of all cytokine genes. Only IL-1 beta rem ains highly expressed at all time-points tested. Overall, these result s provide evidence that healing and non-healing C. albicans i.c. infec tions differ in the immune reaction(s) locally evoked, at least in ter ms of cytokine gene expression, strongly suggesting cytokine involveme nt in the establishment of brain anticandidal resistance.