The Sizes and Shapes of Glycan-Presenting Particles Determine IL-12 Production from Mononuclear Phagocytes via a...

Phagocytosis of microbes through their surface glycans by mononuclear phagocytes (MNPs) is an important process in triggering inflammatory responses and subsequent acquired immunity. However, it is not fully understood how glycan-dependent phagocytosis is related to production of inflammatory cytokines, and especially the production of interleukin (IL)-12, which plays a key role in activation of natural killer cells and differentiation of naive T cells into T helper 1 (Th1). If microbes are considered to be glycan-presenting particles with an appropriate size, assessment of the responses of phagocytic cells to particles with simple glycan chains may provide a new perspective on protective immune responses. In this article, we focus on oligomannose-presenting liposomes (OMLs) and the intact cell wall (ICW) of lactic acid bacteria with preserved shapes and discuss the response of MNPs to these artificial glycan-presenting particles from the perspective of their sizes and shapes. Administration of antigen-encasing OMLs to mice induces a strong antigen-specific cell-mediated immunity that can control the pathological condition of some diseases, accompanied by preferential production of IL-12 from MNPs. Induction of these responses by OMLs relies on oligomannose residues on the liposomes and the sizes of the vesicles. There is a clear threshold particle size of OMLs required to induce IL-12 production and cell-mediated immunity, and these responses are not observed in OMLs with particle sizes <500 nm. In response to stimulation with wall teichoic acid (WTA)-presenting ICWs of Lactobacillus plantarum, bone marrow-derived macrophages secrete significant levels of IL-12 in a WTA-mediated phagocytosis-dependent manner. This ability of ICWs is completely lost by the disruption of ICWs from particulate into filamentous shapes. These findings strongly suggest that the sizes and shapes of specific glycan-presenting particles determine IL-12 production from MNPs through glycan-mediated phagocytosis and define the direction of the immune response. Particle sizes and shapes can influence the spatial organization of glycans on particles required to create molecular assemblies on MNPs, which leads to actin polymerization and subsequent IL-12 production.