Fungal wall-glucans contribution in the local control of inflammation during brain invasion by C.albicans

VIGEZZI C. 1,2, RODRÍGUEZ E.1,2, MIRÓ M.S.1,2, ICELY P.A.1,2, RIERA F.2, CAEIRO J.P.2, GARCIA-EFFRON G.3,4, SOTOMAYOR C.E

Curitiba

Simposio; 15th INFOCUS; 2017

Recognition of beta-glucans from the fungal wall is essential for immune response to C.albicans. These ligands act as immunomodulators according to the site that infect. It has been demonstrated in vitro that the activation of microglia with beta-glucans attenuates the pro-inflammatory response. These molecules are synthesized by1,3-beta-glucan synthase enzyme (GS), whose putative catalytic subunit is FKS1. Mutations in this domain lead to lower production of beta-glucans. Objetive Our objective was to evaluate the role of beta-glucans and their contribution in the modulation of neuroinmmune microenviroment after brain invasion by C.albicans during systemic infection. Methods Male C57BL/6 mice were injected intra venous with 2,5.106C.albicans SC5314 (parental strain) or SC5314-FKS 645 (glucan synthase mutant strain), and at 4 and 12h post-infection(pi) animals were sacrificed and brainsamples were obtained to evaluate fungal burden (CFU), expression of IL-1beta (qPCR), and in situ secretion of proinflammatory cytokine IL-1beta, TNF and anti inflammatory TGF-beta (ELISA). Colony forming units (UFC) in blood and kidney were evaluated for longer times. We also evaluated the ability of the parental and mutant strains to induce cytokine release after incubation with BV2 microglia cell line. Results UFC were similar in blood and kidney in both strains at 4 and 12h pi. At early time point, the brain fungalburden was significantly higher in SC5314 strain than in FKS 645 (p4h, 12h