Phagocytosis: a Synapse for Snaps

RESEARCH HIGHLIGHTS

and a related membrane tyrosine phosphatase, CD148. This suggested that these phosphatases have a posi- tive role in dectin 1 signalling, but can they also show negative effects? Imaging of the contact sites between β-glucan particles and dectin 1‑expressing macrophages revealed that CD45 was uniformly distributed on the surface of resting macrophages, but exposure to β-glucan particles led to clustering of dectin 1 molecules and the formation of phagocytic cups, from which CD45 and CD148 were excluded. The striking ‘bulls-eye’ pattern of staining, characterized by a central PHAGOCYTOSIS dectin 1‑rich signalling region and a peripheral ring area contain- ing the phosphatases, was highly A synapse for snaps reminiscent of the immune synapse structures that form between T cells During T cell activation, antigen particulate β-glucans induced the and APCs. Notably, these phagocytic receptors and adhesion molecules phosphorylation of SYK and strong synapses were also observed when at the interface of the T cell and the dectin 1‑dependent responses in macrophages were exposed to live antigen-presenting cell (APC) are bone marrow-derived macrophages fungi, but not following the binding rearranged into distinct concentric and dendritic cells. However, soluble of soluble glycans to dectin 1. rings; this structure is known as the β-glucans were unable to activate Importantly, macrophage activa- immune synapse and is important signalling responses through dectin 1, tion was inhibited when cells were for promoting activatory signalling. even though they were shown to exposed to plates that were coated Goodridge et al. now report that a bind to this receptor. Additional with both β-glucans and immo- similar structure — which they term experiments using plates or beads bilized CD45‑specific antibodies, the ‘phagocytic synapse’ — forms coated with β-glucans confirmed that indicating that exclusion of CD45 when dectin 1‑expressing phagocytes β-glucans can only activate dectin 1 if phosphatase activity is necessary are exposed to particulate β-glucans they are presented to phagocytes in an for robust dectin 1 signalling in the and is crucial for triggering phago- immobilized form. phagocytic synapse. cytosis and full antimicrobial activity So why then does the presenta- The authors suggest that the in these cells. tion of particulate but not soluble phagocytic synapse serves an Dectin 1 (also known as β-glucans promote dectin 1 activa- important role in allowing dectin 1‑ CLEC7A) is a pattern-recognition tion? During T cell receptor (TCR) expressing phagocytes to discriminate receptor (PRR) that is expressed by activation, the membrane-associated between β-glucan signals that are macrophages, dendritic cells and phosphatase CD45 removes inhibi- delivered from a distance (soluble neutrophils and recognizes β-glucans tory phosphate groups from SRC ligands) and those that are in the present in fungal cell walls. When family kinases to promote their immediate vicinity (immobilized triggered, dectin 1 delivers activatory activation. However, CD45 is subse- on the microbial surface). This may signals to these phagocytes via SRC quently segregated to the periphery ensure that energy-intensive and and SYK family tyrosine kinases of the immune synapse to prevent potentially ‘dangerous’ processes, and an atypical immunoreceptor the removal of activatory phosphate such as phagocytosis and the pro- tyrosine-based activation motif groups from ITAMs associated with duction of reactive oxygen species, (ITAM). The authors were intrigued the TCR signalling complex. The only occur when an invading by the long-standing observation that authors reasoned that such dual microorganism is close at hand. soluble β-glucans can inhibit macro functioning of CD45 could also be Yvonne Bordon phage activation, despite the fact that involved in dectin 1 signalling. In soluble ligands for other PRRs, such keeping with this, they found that ORIGINAL RESEARCH PAPER Goodridge, H. S. as Toll-like receptor family members, activation of dectin 1 by β-glucan et al. Activation of the innate immune receptor Dectin‑1 upon formation of a ‘phagocytic tend to promote robust cell activa- particles was severely compromised synapse’. Nature 472, 471–475 (2011) tion. Exploring this, they found that in macrophages that lacked CD45