Figure 1.

Schematic representation of the fungal cell wall and downstream cellular responses following engagement of Dectin-1 and TLRs on antigen presenting cells (APC). At the top, the interaction between the yeast cell of a fungus, such as C. albicans, is shown as well as the general architecture of the fungal cell wall, consisting of overlapping layers of highly mannosylated proteins, beta glucans (structure within the insert to the right) and chitin. Antigen presenting cells (APCs), including monocytes, macrophages and DCs, engage fungi and activate host responses via several PRRs including the Toll-like receptors (TLR) and Dectin-1. Dectin-1 is alternatively spliced into two functional isoforms, which differ by the presence or absence of a stalk region (shown in dark blue). Dectin-1 recognises linear or branched 1,3-linked β-glucan, which triggers intracellular signalling through at least two pathways, involving Syk kinase and Raf-1, inducing the production of several cytokines, including IL-10, TNF, IL-2, IL-6 and IL-23. TLRs, on the contrary, which recognise various mannosylated and other fungal cell wall structures, signal through the MyD88-Mal mediated NF-κB pathway and induce the production of both pro and anti-inflammatory cytokines, including TNF, IL-10, IL-12 and TGFβ. Co-stimulation of both receptors can amplify the production of cytokines, including TNF, IL-23, IL-10 and IL-6 while downregulating the production IL-12, influencing the resultant generation of adaptive immunity.