Fig. 22

Factors affecting immune functions in dendritic cells and macrophages. A, The immune responses of dendritic cells (DCs) and macrophages are influenced by the physical properties of their surrounding environment, including shape, mechanical forces, surface charge, and multivalency. DCs and macrophages can detect the shape of foreign substances (e.g., viruses) and modify immune signaling accordingly. Mechanical stress activates PIEZO1 ion channels in antigen-presenting cells, leading to calcium influx and cell activation. Natural polysaccharides with cationic charges (e.g., chitosan) can damage mitochondria, causing the release of mitochondrial DNA (mtDNA) and the upregulation of type I interferon responses via the cGAS-STING pathway. Poly-STING agonists activate STING signaling through multivalent interactions that cause STING condensation. B, The physical properties of nanomaterials, such as shape, structure, chirality, size, and multivalency, can affect innate immune signaling in DCs and macrophages. Different shapes and structures of gold nanoparticles can alter pro-inflammatory signaling pathways (nanorods activate NLRP3 inflammasomes; nanospheres and nanocubes induce ROS-mediated inflammation). The chirality of inorganic nanoparticles can also impact immunogenicity by interacting with specific chiral receptors like adhesion G protein-coupled receptors (AGPCRs). Small gold nanoparticles (< 10 nm) stimulate the inflammasome axis, while large gold nanoparticles (> 100 nm) activate NF-κB pathways. Multivalent TLR agonists combined with antigens enhance DC maturation and antigen cross-presentation more efficiently. cGAMP, cyclic GMP–AMP; LLPS, liquid–liquid phase separation; TNF, tumor necrosis factor. Reprint from [130] with a permission from Springer Nature