The role of the cell wall in fungal pathogenesis

Abstract

Fungal infections are a serious health problem. In recent years, basic research is focusing on the identification of fungal virulence factors as promising targets for the development of novel antifungals. The wall, as the most external cellular component, plays a crucial role in the interaction with host cells mediating processes such as adhesion or phagocytosis that are essential during infection. Specific components of the cell wall (called PAMPs) interact with specific receptors in the immune cell (called PRRs), triggering responses whose molecular mechanisms are being elucidated. We review here the main structural carbohydrate components of the fungal wall (glucan, mannan and chitin), how their biogenesis takes place in fungi and the specific receptors that they interact with. Different model fungal pathogens are chosen to illustrate the functional consequences of this interaction. Finally, the identification of the key components will have important consequences in the future and will allow better approaches to treat fungal infections.

Figure 1

Schematic organization of the fungal cell wall. The major structural components are shown. β‐1,3 glucan and chitin are the main structural components located in the inner layer. The outer layer is composed of cell wall proteins (CWPs) that are attached to the inner layer via glycosylphosphatidylinositol (GPI) or internal repeat domains (PIR) linkages.

Figure 2

Receptors involved in the interaction of fungal cell wall components with immune system cells. This figure depicts the multiple receptors that act either alone or simultaneously as sensors for different cell wall components of fungal cells walls. Receptor engagement induces intracellular signals that lead either to endocytosis and phagocytosis signalling or both of them. The receptors are not drawn to scale.

Figure 3

Cell populations of immune system and pattern‐recognition receptors involved in fungal recognition. The main cells of the host innate immune response are monocytes, macrophages, neutrophils and dendritic cells. The receptors expressed by these cell types are shown. TLR, Toll‐like receptors; MR, mannose receptor; FcγR, Fcγ receptor; CR3, complement receptor.

Figure 4

Activation of the complement system via MBL. The figure shows the activation of the complement cascade in response to fungal mannan recognition mediated by MBL. MBL, mannan‐binding lectin; MAC, membrane attack complex.