Immune evasion of C. albicans
Candida albicans responds and modulates host innate as well as adaptive immune reactions. This project aims at elucidating the mechanisms of immune responses by human monocytes and macrophages as well as B cells to Candida. Microbial proteins will be investigated that alone or together with recruited human plasma proteins modulate opsonization, cell interaction and activation. In human plasma, Candida activates all three complement pathways, the alternative, the classical and the lectin pathway. The complement activation product C3b is deposited onto the Candida surface to mark the foreign cells for phagocytosis and for the recognition by different immune cells. C3b and the cleavage products iC3b and C3d are ligands of different cellular receptors. C3b and iC3b are the natural ligands of complement receptors CR3 and CR4 expressed on human monocytes and macrophages. In combination with co-receptors, the monocytes are activated and differentiate into an inflammatory or a regulatory type of macrophage. C3d is the natural ligand of CR2 on B cells and coligation with the B cell antigen results in augmented signaling as a result of the redistribution of the entire coreceptor complex to the lipid rafts. Candida expresses proteins that modulate complement mediated opsonization on different levels and subsequently also the interaction and activation of immune cells. The characterization of the molecular and the cellular interplay, on the level of single molecules and cells, will be carried out and developed into a bioinformatics-based infection model that will offer novel therapeutic targets for treatment.