Contribution of C-type lectin receptor activation, Dectin-1, in the innate immune response against Candida albicans in the central Nervous System

VIGEZZI C; SOTOMAYOR CE

Los Cocos. Cordoba

Otro; Argentinian Spring Course in Advanced Immunology (ASCAI 2013); 2013

International union of Immunology Societies

Invasive C. albicans infections are a serious clinical threat in patients who are immunosuppressed and those who have undergone major surgical procedures, with mortality reaching 30-40% despite the availability of new classes of antifungal drugs. Although the brain and the subarachnoid space have anatomic barriers that protect them, under certain circumstances fungal pathogens are able to get through the blood brain barrier and colonize CNS. In spite of several studies about the pathogenicity of this opportunistic yeast, the mechanism by which this microorganism enters the brain, settles in the parenchyma and interacts with the resident cells is not completely elucidated. In the brain, astrocytes and microglia are considered the innate immune cells involved in the control of microorganisms. Immunity to pathogens critically requires pattern-recognition receptors (PRRs) to trigger intracellular signaling cascades that initiate the immune responses. For Candida, these responses are primarily mediated by Dectin-1, a member of the C-type lectin receptor family (CLR) that recognizes â-glucan present in the fungal wall. This receptor mediates many of effector functions and production of inflammatory mediators, which are critically required for controlling fungal infections. Recently has been proposed that Dectin-1 also can mediate inflammasome activation, a cytoplasmic multimeric complex involved in the processing and activation of IL-1â and IL-18, two cytokines essential for protective antifungal immunity. The aim of this study is to explore the role of Dectin-1 activation during the pathogen-host interaction in CNS and its contribution in the outcome of infection. As astrocytes and microglia are involved in the local innate immune response, we also focused our studies in the mechanism of fungal recognition through â-glucans receptor and its role in glial cells activation.