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

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.

• Authors: Elizabeth C Carroll, Lei Jin, Andres Mori, Natalia Muñoz-Wolf, Ewa Oleszycka, Hannah B T Moran, Samira Mansouri, Craig P McEntee, Eimear Lambe, Else Marie Agger, Peter Andersen, Colm Cunningham, Paul Hertzog, Katherine A Fitzgerald, Andrew G Bowie, Ed C Lavelle
• Journal: Immunity (Immunity) Vol. 44 Issue 3 Pg. 597-608 (Mar 15 2016) ISSN: 1097-4180 [Electronic] United States
• PMID: 26944200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Immunoglobulin G
• Interferon Type I
• Membrane Proteins
• Reactive Oxygen Species
• STING1 protein, human
• Vaccines
• DNA
• Chitosan
• Nucleotidyltransferases
• cGAS protein, human

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Cell Differentiation (drug effects, genetics)
• Cell Movement
• Cells, Cultured
• Chitosan (administration & dosage)
• DNA (metabolism)
• Dendritic Cells (drug effects, physiology)
• Female
• Humans
• Immunity, Cellular (drug effects, genetics)
• Immunoglobulin G (metabolism)
• Interferon Type I (metabolism)
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Knockout
• Mitochondria (metabolism)
• Nucleotidyltransferases (genetics, metabolism)
• Reactive Oxygen Species (metabolism)
• Th1 Cells (immunology)
• Vaccines (administration & dosage)