Comparative Anatomy of Phagocytic and Immunological Synapses

Abstract

The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of "phagocytic synapse." Here, we discuss both types of structures, their organization, and the mechanisms by which they are generated and regulated.

Keywords: actin; endocytosis; exocytosis; immune receptor; immunological synapse; microtubules; phagocytosis; signal transduction.

Figure 1

Schematic representation of the immunological synapse and the phagocytic cup formation. Immunological synapse formation is initiated by the engagement of TCRs on the surface of the T lymphocytes by peptide antigen–MHC complexes on the APC (left). Similarly, engagement of phagocytic receptors by multiple ligand binding on a target particle drives the formation of phagocytic synapses (right). In both settings, receptor engagement leads to F-actin polymerization and membrane deformation at contact sites. Polarization of the MTOC and microtubule network toward at the IS are important for the delivery of vesicles containing cytokines or lytic enzymes in helper or cytotoxic T cells, respectively, but also to deliver TCR-signaling components during immunological synapse formation. Microtubules also contribute to F-actin remodeling in complement-mediated phagocytosis. Internalization of cell surface TCRs by endocytosis and their focal recycling participate in the regulation of T cell activation. Finally, in either system, triggering of multiple signaling pathways downstream of the surface receptors leads to de novo transcriptional programs controlling cell survival, activation, and cytokine production.