C-type lectins and phagocytosis

Abstract

To recognise and respond to pathogens, germ-line encoded pattern recognition receptors (PRRs) bind to conserved microbial structures and activate host defence systems, including microbial uptake by phagocytosis. Phagocytosis is a complex process that is instrumental in the control of extracellular pathogens, and this activity is mediated by several PRRs, including a number of C-type lectins. While some of these receptors have clearly been shown to mediate or regulate the uptake of pathogens, others are more contentious and are less well understood in terms of their phagocytic potential. Furthermore, very little is known about the underlying phagocytic mechanisms. Here, we review the phagocytic roles of the mannose receptor, Dectin-1, dendritic cell-specific ICAM grabbing non-integrin (DC-SIGN), DCL-1, mannose binding lectin and surfactant proteins A and D.

Fig. 1

Direct recognition, opsonisation, complement activation and receptor up-regulation by C-type lectins. Phagocytic C-type lectins can directly recognise PAMPs on the surface of microbes and mediate phagocytosis (e.g. Dectin-1). Alternatively, soluble C-type lectins can interact directly with pathogens to promote opsonisation of the microbe (e.g. MBL) which can subsequently be phagocytosed via specific receptors. In addition, some C-type lectins can activate complement leading to its deposition on the microbial surface and phagocytosis mediated by complement receptors (e.g. MBL associated MASPS are activated on binding to pathogens which in turn cleave complement components and activate the complement system). Finally, C-type lectins can cause up-regulation of other phagocytic receptors, independently of their binding to the microbe (e.g. MBL up-regulation of SR-A).

Fig. 2

Schematic representation of Fc$\gamma$R signalling leading to recruitment of Syk, activation of Rac, Cdc42 and PI3-kinase, and engulfment of microbe via “zippered” phagocytosis.

Fig. 3

Structural representation of C-type lectin proteins. Mannose receptor (“bent” conformation), Dectin-1, DCL-1 and oligomers of DC-SIGN, mannose binding lectin and surfactant protein-D are shown. Not drawn to scale.