UC Irvine

Toll-like receptors (TLRs) on innate immune cells are important in the early detection of pathogens and initiation of immune responses. Spatial and temporal aspects of signaling via these receptors are critical in defining unique and effective immune responses. These factors, however, are not well-characterized and there are currently no methods yet to probe them. Herein, I describe approaches developed by the Esser-Kahn lab to address spatial and temporal activation of immune pathways. We have designed photo-labile immunostimulants for controlled activation of cells in space and time. Variants of pyrimido indoles (TLR4 agonist), imidazoquinolines (TLR7 and 8 agonists), and palmitylated-peptides (TLR1, 2, and 6 agonist) were generated with photo-labile protecting groups installed at moieties necessary for productive receptor interaction. We demonstrate controlled activation using light of the NF-κB pathway in RAW macrophages, bone marrow-derived dendritic cells, and TLR-bearing fibroblasts.