Silencing of and Shows the Importance of -Linked Glycosylation During the -Host Interaction.

is a pathogenic fungus of worldwide distribution and one of the etiological agents of sporotrichosis. The cell wall is the first point of contact with host cells; therefore, its composition has been widely studied. It has a cell wall composed of chitin, β-glucans, and glycoproteins modified with linked and linked glycans. Protein linked glycosylation is mediated by two gene families, and Therefore, we evaluated the relevance of protein linked glycosylation during the interaction of with the host. Independent silencing of the and was accomplished by interference RNA. Morphological analyses revealed defects in cell morphology in both yeast and mycelial cells; however, these defects differed between and silencing. Subsequently, the cell wall was characterized, and the silencing of these genes markedly changed cell wall organization. When the silenced strains interacted with human peripheral blood mononuclear cells, a reduced ability to stimulate the proinflammatory cytokines IL-6 and TNFα was found. However, the silenced mutants also stimulated higher levels of IL-10 and IL-1β. Interaction with macrophages and neutrophils was also altered, with increased phagocytosis and decreased extracellular trap formation in both sets of silenced strains. Survival assays in larvae showed that silencing of any of these genes reduced the ability of to kill the host. In addition, the mutant strains showed defects in the adhesion to extracellular matrix proteins. These data indicate that and are relevant for cell wall synthesis and interaction with the host.