Fungal-derived immune modulating molecules.

Invasive fungal infections are an increasing clinical problem for which new therapeutic approaches are needed. Understanding the initial interaction between fungi and the host offers potential for development of new drugs or vaccines. It has recently been recognized that like other pathogens, fungi initially interact with the innate immune system via binding between fungus-specific chemical signatures (pattern-associated molecular patterns or PAMPs) and pattern recognition receptors (PRRs) on mononuclear phagocytes. Fungal PAMPs are restricted to complex carbohydrates in the cell wall, including mannoproteins, phospholipomannan, beta-glucans and possibly chitin. These PAMPs bind specifically to two classes of PRR in phagocyte membranes, toll-like receptors and C-lectin-like receptors, through which they initiate signaling responses that culminate in release of pro- and anti-inflammatory cytokines, link the innate immune response with the adaptive immune response and initiate phagocytosis and intracellular killing. Isolated PAMPs have been used to dissect phagocyte responses in vitro and have revealed mechanisms by which host cells can tailor innate immune responses to individual pathogens. The interactions are complex and are yet to be translated into a clear understanding of the roles of the respective PAMPs and PRRs in vivo. Recent advances in this area in relation to the pathogenesis of fungal infections are summarized in this chapter.