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

VIGEZZI C; RODRIGUEZ E; MIRÓ MS; ICELY PA; RIERA F; CAEIRO JP; GARCÍA-EFFRON G; SOTOMAYOR CE

Curitiba

Congreso; XV Forum on Fungal Infection in the Clinical Practice, INFOCUS 2017; 2017

INFOCUS

IntroductionRecognition 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 by 1,3-beta-glucan synthase enzyme (GS), whose putative catalytic subunit is FKS1. Mutations in this domain lead to lower production of beta-glucans.ObjetiveOur 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. MethodsMale C57BL/6 mice were injected intra venous with 2,5.106 C.albicans SC5314 (parental strain) or SC5314-FKS 645 (glucan synthase mutant strain), and at 4 and 12h post-infection(pi) animals were sacrificed and brain samples 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.ResultsUFC were similar in blood and kidney in both strains at 4 and 12h pi. At early time point, the brain fungal burden was significantly higher in SC5314 strain than in FKS 645 (p4h, 12h