Systemic infection by Candida albicans triggers early immunological response in the brain: modulation of innate receptors and immune mediators in resident glial cells.

VIGEZZI, CECILIA; MIRÓ, MARÍA SOLEDAD; ICELY, PAULA ALEJANDRA; RODRIGUEZ, EMILSE; CEJAS, HUGO; SOTOMAYOR, CLAUDIA ELENA

Buenos Aires

Congreso; LXIII Argentinian Immunology Society Meeting; 2015

Argentinian Immunology Society Meeting

Interleukin-1beta (IL-1beta) is a key pro-inflammatory factor in innate antifungal immunity. Glucan receptor Dectin-1 is essential for antifungal response to Candida albicans and it is necessary for the beta-glucans-induced IL-1beta secretion through NALP3 inflammasome in the periphery, but little is known about its expression during Central Nervous System (CNS) infections. Our objective was to evaluate the inflammatory response of resident glial cells and the contribution of these receptors during C.albicans CNS infection. Male C57BL/6 mice were injected iv with 2,5.106 intra venous C.albicans (SC5314) and at 4,12,24 and 48h post-infection(pi), animals were sacrificed and blood, kidney and brain samples were obtained to evaluate fungal burden(CFU), histological changes(PAS and HE stain) expression of Dectin-1, NALP3 and IL-1beta (PCR), and in situ cytokines secretion (IL-1beta,IL6,TNF-alpha,IL-10,TGFbeta,ELISA). In vitro expression of these molecules in Bv2 microglial line after fungus contact also was studied. Fungemia was highest at 4h, time in which the fungus was recovered from the brain (CFU-p<0.05); at 12h pi, hyphae of C.albicans in absence of inflammatory infiltrate were visualized. At early times pi, local IL-1beta secretion was significantly increased compared to uninfected control (p<0.05), whereas its mRNA undergoes a down-regulation (p<0.05). Interestingly, the expression of NALP3 was unchanged at 4h and 12h pi. Immediately after fungus arrives to the brain, Dectin-1 transcription was down-regulated, recovering basal levels at 12h pi. In vitro expression of Dectin-1 in microglial cells decreased after fungus contacts. This study contribute to the understanding the fine tuning triggered by C.albicans in the early stages of CNS infection.