Phagocytosis and antigen presentation: A partnership initiated by Toll-like receptors

Professional phagocytes play an important role in the clearance of microbial pathogens and apoptotic cells. Many receptors are involved in this process, some with signalling capabilities, some without. Increasing evidence now shows a previously unappreciated regulatory component to phagocytosis exerted by the concomitant engagement of signalling receptors. The engagement of Toll-like receptors (TLRs) during phagocytosis of microbial pathogens is the best characterised example. Here, a brief overview is presented of the findings that TLRs exert positive and phagosome autonomous control on both the kinetics and outcomes of phagosome maturation. Although phagosomes could mature in the absence of TLR signals, they did so at a slower constitutive rate. Engagement of TLRs from another phagosome or from the plasma membrane did not affect the constitutive maturation of phagosomes devoid of TLR ligands. This was also reflected in the superior ability of phagosomes carrying TLR ligands to contribute peptides to major histocompatibility complex (MHC) class II molecules. Thus, TLR control of antigen presentation favours the presentation of microbial antigens within the context of T-lymphocyte costimulatory molecule expression. This current work aims to identify whether TLRs exert similar control on the presentation of phagocytosed antigens within MHC class I molecules, a process referred to as cross-presentation.