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

VIGEZZI, CECILIA; RODRIGUEZ, EMILSE; MIRÓ, MARÍA SOLEDAD; ICELY, PAULA ALEJANDRA; RIERA, FERNANDO OSCAR; CAEIRO, JUAN PABLO; GARCÍA EFFRON, GUILERMO; SOTOMAYOR, CLAUDIA ELENA

Congreso; 15th INFOCUS; 2017

Recognition of beta-glucans from the fungal wall by Dectin-1 receptor 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 b-glucans attenuates the pro-inflammatory response. These molecules are synthesized by 1,3-b-glucan synthase enzyme (GS), whose putative catalytic subunit is FKS1. Mutations in this domain lead to lower production of beta-glucans. Our objective was to evaluate the contribution of fungal wall b-glucans in inmmune brain modulation after systemic infection by C.albicans. For that purpose we used C.albicans SC5314, parental strain (WT) and C.albicans FKS645 strain with low expression of b-glucans (GS defective strain mutation). C. albicans strains infected the brain at 4h after systemic infection; at 12h fungus was observed in brain, in absence of inflammatory infiltrate.Resident cells induce an early increase of the pro-inflammatory cytokines.C.albicans FKS645 strain (b-glucans poor expression) led to early increased inflammatory mediator, which could explain the lower fungal load observed.Higher levels of anti-inflammatory TGFb were found with C.albicans FKS645, and was maintained at the time studied.In vitro assays showed high levels of TNFa after infection, being higher in the defective strain.The poor dectin-1 activation pathway, promotes a robust pro-inflammatory reaction in brain that could be relevant to control the fungal growth. The increased levels of anti-inflammatory cytokines could be involved in the protection of the brain from tissue damage associated to C.albicans infection.