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 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.
Barluzzi
R
R
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Mazzolla
R
R
Brozzetti
A
A
Puliti
M
M
Mariucci
G
G
Mosci
P
P
Bistoni
F
F
Blasi
E
E
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology*; D000917:Antibody Formation; D001921:Brain / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D002176:Candida albicans / Q000472:pathogenicity* / Q000502:physiology*; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000502:physiology; D016207:Cytokines / Q000235:genetics; D004198:Disease Susceptibility; D015870:Gene Expression / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology; D007109:Immunity / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000235:genetics; D010431:Pentoxifylline / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D014158:Transcription, Genetic
D000908:Antibodies, Fungal; D016207:Cytokines; D006146:Guanidines; D019001:Nitric Oxide Synthase; C004479:pimagedine; D010431:Pentoxifylline