Dectin-1 pathway activation is important to Cryptococcus neoformans killing (67.10)

Abstract

Abstract Cryptococcus neoformans (Cn) is an encapsulated yeast that causes life-threatening meningoencephalitis in immunocompromised patients. The infectious propagules are inhaled into the host’s lug and interact with alveolar macrophages. An adequate pattern of macrophage activation is crucial to the outcome of the infection. However, it has been very difficult to demonstrate macrophage fungicidal activity in vitro. The main goal of this work was to determine if differential activation of macrophages by the dectin-1 pathway could increase Cn killing and improve host survival. Peritoneal macrophages were stimulated with zymozan and co-cultured ex vivo with opsonized Cn (H99) to allow phagocytosis. Our results showed that after zymozan stimulation of macrophages, fungal killing was increased. Stimulation with zymosan was more effective in fungal killing than stimulation with depleted-zymosan. Blockade of dectin-1 receptor reverted fungal killing to control levels only in macrophages stimulated with depleted zymozan. The ROS production was lower than in control groups. There was also a higher acidification of endosomes in zymozan-stimulated groups. Taken together, the data suggests that dectin-1 pathway activation by zymozan contributes to Cn killing. However, for the interaction between encapsulated C. neoformans cells and macrophages dectin-1 stimulation may be inadequate because the polysaccharide capsule blocks access to cell wall structures that trigger the dectin-1 receptor.