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

被引：491

作者：

Carroll, Elizabeth. C. ^{[1
]}

Jin, Lei ^{[2
]}

Mori, Andres ^{[1
]}

Munoz-Wolf, Natalia ^{[1
]}

Oleszycka, Ewa ^{[1
]}

Moran, Hannah B. T. ^{[1
]}

Mansouri, Samira ^{[2
]}

McEntee, Craig P. ^{[1
]}

Lambe, Eimear ^{[1
]}

Agger, Else Marie ^{[3
]}

Andersen, Peter ^{[3
]}

Cunningham, Colm ^{[6
,7
]}

Hertzog, Paul ^{[4
,5
]}

Fitzgerald, Katherine A. ^{[8
,9
]}

Bowie, Andrew G. ^{[10
]}

Lavelle, Ed C. ^{[1
,11
,12
]}

机构：

[1] Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Adjuvant Res Grp, Dublin D02 PN40 2, Ireland

[2] Albany Med Coll, Ctr Immunol & Microbial Dis, 47 New Scotland Ave,MC 151, Albany, NY 12208 USA

[3] Statens Serum Inst, Dept Infect Dis Immunol, Artillerivej 5, DK-2300 Copenhagen S, Denmark

[4] Monash Univ, MIMR PHI, Ctr Innate Immun & Infect Dis, Clayton, Vic 3068, Australia

[5] Monash Univ, Dept Mol & Translat Sci, Clayton, Vic 3068, Australia

[6] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin D02 PN40 2, Ireland

[7] Trinity Coll Dublin, Trinity Coll Inst Neurosci, Dublin D02 PN40 2, Ireland

[8] Univ Massachusetts, Sch Med, Dept Med, Program Innate Immun,Div Infect Dis & Immunol, Worcester, MA 01605 USA

[9] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Ctr Mol Inflammat Res, N-7491 Trondheim, Norway

[10] Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Viral Immune Evas Grp, Dublin D02 PN40 2, Ireland

[11] Trinity Coll Dublin, CRANN, Dublin D02 PN40 2, Ireland

[12] Trinity Coll Dublin, Adv Mat Bioengn Res Ctr AMBER, Dublin D02 PN40 2, Ireland

来源：

IMMUNITY | 2016年 / 44卷 / 03期

基金：

爱尔兰科学基金会;

关键词：

DOUBLE-STRANDED-RNA; MURINE B-CELLS; DENDRITIC CELLS; INNATE IMMUNITY; IFN-GAMMA; INFLAMMASOME; TUBERCULOSIS; RESPONSES; MODULATION; ACTIVATION;

D O I：

10.1016/j.immuni.2016.02.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：597 / 608

页数：12

共 45 条

[1] Adjuvant modulation of the cytokine balance in Mycobacterium tuberculosis subunit vaccines;: immunity, pathology and protection [J].

Agger, Else Marie ;

Cassidy, Joseph P. ;

Brady, Joseph ;

Korsholm, Karen S. ;

Vingsbo-Lundberg, Carina ;

Andersen, Peter .

IMMUNOLOGY, 2008, 124 (02) :175-185

[2] The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo [J].

Blaauboer, Steven M. ;

Mansouri, Samira ;

Tucker, Heidi R. ;

Wang, Hatti L. ;

Gabrielle, Vincent D. ;

Jin, Lei .

ELIFE, 2015, 4 :1-25

[3] IFN-GAMMA ENHANCES SECRETION OF IGG2A FROM IGG2A-COMMITTED LPS-STIMULATED MURINE B-CELLS - IMPLICATIONS FOR THE ROLE OF IFN-GAMMA IN CLASS SWITCHING [J].

BOSSIE, A ;

VITETTA, ES .

CELLULAR IMMUNOLOGY, 1991, 135 (01) :95-104

[4]

Brewer JM, 1999, J IMMUNOL, V163, P6448

[5] Spectrum and Mechanisms of Inflammasome Activation by Chitosan [J].

Bueter, Chelsea L. ;

Lee, Chrono K. ;

Wang, Jennifer P. ;

Ostroff, Gary R. ;

Specht, Charles A. ;

Levitz, Stuart M. .

JOURNAL OF IMMUNOLOGY, 2014, 192 (12) :5943-5951

[6] Chitosan but Not Chitin Activates the Inflammasome by a Mechanism Dependent upon Phagocytosis [J].

Bueter, Chelsea L. ;

Lee, Chrono K. ;

Rathinam, Vijay A. K. ;

Healy, Gloria J. ;

Taron, Christopher H. ;

Specht, Charles A. ;

Levitz, Stuart M. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (41) :35447-35455

[7] STING is a direct innate immune sensor of cyclic di-GMP [J].

Burdette, Dara L. ;

Monroe, Kathryn M. ;

Sotelo-Troha, Katia ;

Iwig, Jeff S. ;

Eckert, Barbara ;

Hyodo, Mamoru ;

Hayakawa, Yoshihiro ;

Vance, Russell E. .

NATURE, 2011, 478 (7370) :515-U111

[8] The cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling [J].

Cai, Xin ;

Chiu, Yu-Hsin ;

Chen, Zhijian J. .

MOLECULAR CELL, 2014, 54 (02) :289-296

[9] Vaccine Adjuvants: Putting Innate Immunity to Work [J].

Coffman, Robert L. ;

Sher, Alan ;

Seder, Robert A. .

IMMUNITY, 2010, 33 (04) :492-503

[10] Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination [J].

Desmet, Christophe J. ;

Ishii, Ken J. .

NATURE REVIEWS IMMUNOLOGY, 2012, 12 (07) :479-491

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