Interaction Dectin-1/beta-glucans in brain: delicate balance between controlling inflammation and fungal control.

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

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Glucan receptor Dectin-1 is essential for antifungal response to Candida albicans in the periphery, but little is known about its role during Central Nervous System (CNS) infections. -glucans are widely recognized as immunomodulators. It has been demonstrated in vitro that the activation of microglia through Dectin-1 attenuates the production of proinflammatory cytokines. Our objective was to evaluate the role of this interaction in brain during C.albicans systemic infection. Male C57BL/6 mice were injected with 2,5.106 intra venous C.albicans SC5314 (parental) or SC5314-FKS 645 (glucan synthase mutant strain), 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), expression of Dectin-1 and IL-1beta (IL-1beta) (qPCR), and in situ cytokines secretion (IL-1beta, IL6, TNF-alpha, ELISA). Dectin-1 deficient mice (KO) were infected with SC5314 and killed at 4h and 12h. In both strain, fungemia was highest at 4h pi (CFU-p<0.05). Profile of infection of each strain was different. At early time point, the fungal burden was significantly higher in SC5314 strain than in FKS 645 (p4h, 12h <0.05). Interestingly, at 4h pi SC5314 WT infection did not induce proinflammatory cytokines secretion, whereas in infection with FKS-645, local IL-1beta and TNFalfa secretion was significantly increased (p<0.05). TNFalfa production in Dectin-1KO was significantly higher than in WT animals (p<0.05), while increasing IL-1b was observed as a trend. We also evaluated the ability of the parental and mutant strain to induce cytokine release after incubation with BV2 microglia cell line. IL-1beta levels were undetectable at 24h, while higher TNFalfa release was observed (p<0.05). The absence or decrease of Dectin-1 pathway, promotes a robust proinflammatory reaction in brain that could be relevant to control the fungal growth. This study provides evidences about the immunomodulatory mechanisms of beta-glucans in brain.