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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146 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

Cite this

Carroll, E. C., Jin, L., Mori, A., Muñoz-Wolf, N., Oleszycka, E., Moran, H. B. T., ... Lavelle, E. C. (2016). The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons. Immunity, 44(3), 597-608. https://doi.org/10.1016/j.immuni.2016.02.004
Carroll, Elizabeth C. ; Jin, Lei ; Mori, Andres ; Muñoz-Wolf, Natalia ; Oleszycka, Ewa ; Moran, Hannah B.T. ; Mansouri, Samira ; McEntee, Craig P. ; Lambe, Eimear M ; Agger, Else Marie ; Andersen, Peter ; Cunningham, Colm ; Hertzog, Paul ; Fitzgerald, Katherine A ; Bowie, Andrew G ; Lavelle, Ed C. / The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons. In: Immunity. 2016 ; Vol. 44, No. 3. pp. 597-608.
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title = "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.",
author = "Carroll, {Elizabeth C.} and Lei Jin and Andres Mori and Natalia Mu{\~n}oz-Wolf and Ewa Oleszycka and Moran, {Hannah B.T.} and Samira Mansouri and McEntee, {Craig P.} and Lambe, {Eimear M} and Agger, {Else Marie} and Peter Andersen and Colm Cunningham and Paul Hertzog and Fitzgerald, {Katherine A} and Bowie, {Andrew G} and Lavelle, {Ed C}",
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Carroll, EC, Jin, L, Mori, A, Muñoz-Wolf, N, Oleszycka, E, Moran, HBT, Mansouri, S, McEntee, CP, Lambe, EM, Agger, EM, Andersen, P, Cunningham, C, Hertzog, P, Fitzgerald, KA, Bowie, AG & Lavelle, EC 2016, 'The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons', Immunity, vol. 44, no. 3, pp. 597-608. https://doi.org/10.1016/j.immuni.2016.02.004

The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons. / Carroll, Elizabeth C.; Jin, Lei; Mori, Andres; Muñoz-Wolf, Natalia; Oleszycka, Ewa; Moran, Hannah B.T.; Mansouri, Samira; McEntee, Craig P.; Lambe, Eimear M; Agger, Else Marie; Andersen, Peter; Cunningham, Colm; Hertzog, Paul; Fitzgerald, Katherine A; Bowie, Andrew G; Lavelle, Ed C.

In: Immunity, Vol. 44, No. 3, 15.03.2016, p. 597-608.

Research output: Contribution to journalArticleResearchpeer-review

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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

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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.

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