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

Elizabeth C. Carroll, Lei Jin, Andres Mori, Natalia Muñoz-Wolf, Ewa Oleszycka, Hannah B.T. Moran, Samira Mansouri, Craig P. McEntee, Eimear M Lambe, Else Marie Agger, Peter Andersen, Colm Cunningham, Paul Hertzog, Katherine A Fitzgerald, Andrew G Bowie, Ed C Lavelle

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213 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)597-608
Number of pages12
JournalImmunity
Volume44
Issue number3
DOIs
Publication statusPublished - 15 Mar 2016

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