The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons

The cationic polysaccharide chitosan is an attractive candidate adjuvant capable of driving potent cell-mediated immunity, but the mechanism by which it acts is not clear. We show that chitosan promotes dendritic cell maturation by inducing type I interferons (IFNs) and enhances antigen-specific T helper 1 (Th1) responses in a type I IFN receptor-dependent manner. The induction of type I IFNs, IFN-stimulated genes and dendritic cell maturation by chitosan required the cytoplasmic DNA sensor cGAS and STING, implicating this pathway in dendritic cell activation. Additionally, this process was dependent on mitochondrial reactive oxygen species and the presence of cytoplasmic DNA. Chitosan-mediated enhancement of antigen specific Th1 and immunoglobulin G2c responses following vaccination was dependent on both cGAS and STING. These findings demonstrate that a cationic polymer can engage the STING-cGAS pathway to trigger innate and adaptive immune responses. [Display omitted] •The adjuvant chitosan promotes DC maturation by inducing type I interferons•Chitosan-triggered type I interferons and DC maturation requires cGAS and STING•ROS and cytoplasmic DNA are necessary for chitosan to drive type I interferons•Promotion of Th1 responses by chitosan requires IFNAR, cGAS, and STING Adjuvants are essential in many vaccines to promote innate and adaptive immunity. However, our limited understanding of their mode(s) of action is an obstacle to progress. Lavelle and colleagues demonstrate that the cationic polysaccharide chitosan activates dendritic cells and promotes Th1 responses by engaging the DNA sensor cGAS-STING pathway.