| Literature DB >> 26944200 |
Elizabeth C Carroll1, Lei Jin2, Andres Mori1, Natalia Muñoz-Wolf1, Ewa Oleszycka1, Hannah B T Moran1, Samira Mansouri2, Craig P McEntee1, Eimear Lambe1, Else Marie Agger3, Peter Andersen3, Colm Cunningham4, Paul Hertzog5, Katherine A Fitzgerald6, Andrew G Bowie7, Ed C Lavelle8.
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.Entities:
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Year: 2016 PMID： 26944200 PMCID： PMC4852885 DOI： 10.1016/j.immuni.2016.02.004
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745