TY - JOUR
T1 - The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons
AU - Carroll, Elizabeth C.
AU - Jin, Lei
AU - Mori, Andres
AU - Muñoz-Wolf, Natalia
AU - Oleszycka, Ewa
AU - Moran, Hannah B.T.
AU - Mansouri, Samira
AU - McEntee, Craig P.
AU - Lambe, Eimear M
AU - Agger, Else Marie
AU - Andersen, Peter
AU - Cunningham, Colm
AU - Hertzog, Paul
AU - Fitzgerald, Katherine A
AU - Bowie, Andrew G
AU - Lavelle, Ed C
PY - 2016/3/15
Y1 - 2016/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84960415391&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2016.02.004
DO - 10.1016/j.immuni.2016.02.004
M3 - Article
C2 - 26944200
AN - SCOPUS:84960415391
SN - 1074-7613
VL - 44
SP - 597
EP - 608
JO - Immunity
JF - Immunity
IS - 3
ER -
