Detection of fungal particles by Dectin-1 triggers reorganization of macrophage membrane proteins to form a “phagocytic synapse” (134.35)

Abstract

Abstract The β-glucan receptor Dectin-1 is a central player in the anti-fungal responses of myeloid phagocytes. Detection of β-glucan-containing particles by Dectin-1, which signals via an ITAM-like motif in its cytoplasmic tail, triggers phagocytosis, the induction of an oxidative burst, and production of a variety of inflammatory mediators by macrophages and dendritic cells. In contrast, soluble β-glucans, which are too small to trigger phagocytosis, fail to activate Dectin-1 signaling. However, soluble β-glucans immobilized on latex beads are capable of inducing Dectin-1-mediated responses. We used immunofluorescence microscopy to study the rearrangement of macrophage surface proteins upon binding of β-glucan particles to Dectin-1, and observed the formation of a synapse analogous to the immunological synapse that forms between a T cell and an antigen presenting cell. Our data indicate that the formation of this "phagocytic synapse" is required to initiate Dectin-1 signaling, and that the inability of soluble β-glucans to trigger such reorganization accounts for their failure to activate Dectin-1 signaling. This work is supported by grants to DMU from the NIH (AI071116, GM085796) and AHA (0640100N); HSG is a CCFA Research Fellow