Astrocytes- Candida albicans interaction: cytokines profiles, nitric oxide production and TLR-2 expression.

FIGUEREDO CM; RENNA MS; SOTOMAYOR CE

Rio de Janeiro

Congreso; 13 th Internacional Congress of Immunology.; 2007

ALAI

ASTROCYTES-CANDIDA ALBICANS INTERACTION: CYTOTOKINES PROFILE, NITRIC OXIDE PRODUCTION AND TLR-2 EXPRESSION. Figueredo C M, Renna M S, Sotomayor C E. Inmunolog¨ªa. Dto Bioq. Cl¨ªnica (CIBICI-CONICET).Facultad de Ciencias Qu¨ªmicas.Universidad Nacional de C¨®rdoba. Upon central nervous system(CNS) injury, the astrocyte(As) activation status could be rapidly modified. The mechanisms that underlie the activation of As by the pathogens and their consequences for infection have not been elucidated. We reported that during Candida albicans CNS infection, the fungus triggered a particular mRNA profile of early-cytokine and that the As are actively involved. Here we explored the ability of fungus to stimulate As in resting or activated conditions. C6 astroglial-line were co-cultured(24h) with different stimulus: viable C.albicans(5:1 E:T ratio), TNF-¦Á, LPS+ TNF-¦Á and LPS+ TNF-¦Á+C.albicans. Low expression levels of mRNA-encoding proinflammatory cytokines IL-1¦Â, TNF-¦Á and IL-6 were detected after fungus contact, meanwhile immune-stimulated As strongly upregulated the levels of transcript; in this condition activated-As markedly responded against pathogen. Interestingly, the mRNA expression of anti-inflammatory cytokine IL-10 evaluated in kinetic studies(3h, 6h, 12h) revealed a clear and progressive increased after C.albicans incubation. During in vivo activation of As, the overproduction of NO could be involved in neuronal injury or fungal control. In vitro activated-As produced significant NO concentrations(p<0,01); meanwhile in resting-As C.albicans per se triggered the nitrite release(p<0,01), in activated-As the fungus down modulated the total response. Finally we evaluated the presence of TLR-2 receptor involved in fungal recognition. We detected low-level constitutive expression of mRNA-encoding TLR-2 and protein receptor in resting-As. Importantly, this molecule was markedly elevated following exposure to C.albicans. Similar pattern was found in activated¨CAs. These results indicate potentially importance and a new role of As during the progression of CNS C.albicans infection. Candida albicans CNS infection, the fungus triggered a particular mRNA profile of early-cytokine and that the As are actively involved. Here we explored the ability of fungus to stimulate As in resting or activated conditions. C6 astroglial-line were co-cultured(24h) with different stimulus: viable C.albicans(5:1 E:T ratio), TNF-¦Á, LPS+ TNF-¦Á and LPS+ TNF-¦Á+C.albicans. Low expression levels of mRNA-encoding proinflammatory cytokines IL-1¦Â, TNF-¦Á and IL-6 were detected after fungus contact, meanwhile immune-stimulated As strongly upregulated the levels of transcript; in this condition activated-As markedly responded against pathogen. Interestingly, the mRNA expression of anti-inflammatory cytokine IL-10 evaluated in kinetic studies(3h, 6h, 12h) revealed a clear and progressive increased after C.albicans incubation. During in vivo activation of As, the overproduction of NO could be involved in neuronal injury or fungal control. In vitro activated-As produced significant NO concentrations(p<0,01); meanwhile in resting-As C.albicans per se triggered the nitrite release(p<0,01), in activated-As the fungus down modulated the total response. Finally we evaluated the presence of TLR-2 receptor involved in fungal recognition. We detected low-level constitutive expression of mRNA-encoding TLR-2 and protein receptor in resting-As. Importantly, this molecule was markedly elevated following exposure to C.albicans. Similar pattern was found in activated¨CAs. These results indicate potentially importance and a new role of As during the progression of CNS C.albicans infection. Trabajo seleccionado por el Comit¨¦ Cientifico y distinguido con Beca de Asistencia al Congreso.