Engineering Supramolecular Organizing Centers for Optogenetic Control of Innate Immune Responses

The spatiotemporal organization of oligomeric protein complexes, such as the supramolecular organizing centers (SMOCs) made of MyDDosome and MAVSome, is essential for transcriptional activation of host inflammatory responses and immunometabolism. Light-inducible assembly of MyDDosome and MAVSome is presented herein to induce activation of nuclear factor-kB and type-I interferons. Engineering of SMOCs and the downstream transcription factor permits programmable and customized innate immune operations in a light-dependent manner. These synthetic molecular tools will likely enable optical and user-defined modulation of innate immunity at a high spatiotemporal resolution to facilitate mechanistic studies of distinct modes of innate immune activations and potential intervention of immune disorders and cancer.