DECTIN-1 PATHWAY-MEDIATED IMMUNOMODULATION IN THE LOCAL RESPONSE DURING Candida albicans BRAIN INFECTION

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

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

-glucans of the fungal wall are recognized by Dectin-1 receptor. This interaction is essential for immune response to C.albicans in the periphery, but little is known about its role during Central Nervous System infections. -glucans are widely recognized as immunomodulators, and it has been proved in vitro that the activation of microglia through Dectin-1 attenuates the proinflammatory response. Our aim was to evaluatethe role of Dectin-1 recognition in brain, during C.albicanssystemic infection. Male C57BL/6 (WT) and Dectin-1 deficient (KO) mice were injected intravenously with C.albicans SC5314 (2.5x106 yeast), and at 4, 12, 24 and 48h post-infection (pi) the animals were sacrificed. The fungal burden (CFU) was studied in blood, kidney and brain homogenates. An early colonization was observed in the periphery as well as in brain(p4h<0.05). Brain innate immune response was assessed at early times, in order to study the contribution of resident cells. At 4 and 12h, Dectin-1 and IL-1 expression (qPCR), in situ pro- and anti-inflammatory cytokines secretion (IL-1,IL-6,TNF,IL-10,TGF)(ELISA), histopathological and microgliosis/astrogliosis studies were performed. The fungal burden was higher in WT than KO mice(p<0.05). Interestingly, infection in WT mice does not induce proinflammatory cytokines secretion at 4h, while a significant increase was observed in KO mice with sustained levels at 12h. Local IL-1 and TNF secretion in KO mice was significantly higher than in WT animals at 4h(p<0.05). Moreover, the IL-1 mRNA decreased at 12h pi in WT(p<0.05) but not in KO mice. TGF production was downregulated after the infection in WT(p4h,12h<0.05) but not modified in KO mice. When TGF secretion between groups was compared, significant differences were observed(p<0.05).This study provides new evidences about the role of Dectin-1 in immunomodulatory mechanisms developed in the brain in order to moderate the delicate balance between inflammation and fungal control.