Efeito da suplementação de glicose em células epiteliais brônquicas humanas infectadas com Cryptococcus neoformans

Abstract

Hyperglycemia may be a risk factor for cryptococcal meningitis in immunocompetent individuals. A model frequently used to understand cellular changes in diabetes consists of exposure to high glucose concentrations in vitro. In the airways, epithelial cells are crucial for the establishment of cryptococcosis. The effects of the combination of Cryptococcus neoformans and glucose concentrations (5 mM or 15 mM) on human bronchial epithelial cells (BEAS-2B) for 24 h were evaluated. In trypan blue assays, no cytotoxic effects were observed in cells stimulated by C. neoformans and/or treated with glucose supplementation. C. neoformans increased the production of IL-6 and IL-8, but not IL-10, when compared to the control group. In contrast to the increased IL-6 production and STAT3 activation directly proportional to the increase in glucose dose, IL-8 production and ERK1/2 activation were decreased in C. neoformans treatments supplemented with 5 mM or 15 mM glucose when compared with the treatment containing only C. neoformans. Furthermore, glucose supplementation increased the internalization of C. neoformans into BEAS-2B cells, and reduced the percentage of C. neoformans on the surface and its growth. Glucose supplementation promoted proinflammatory responses in bronchial epithelial cells infected with C. neoformans by increasing IL-6 production and phospho-STAT3 activation, and decreasing IL-8 production and ERK1/2 phosphorylation. IL-6 is crucial for controlling the acute phase protein response of inflammation and notably increases the level of p-STAT3, which may be involved in the regulation of cellular inflammation.