Journal ArticleDOI
DNA released from dying host cells mediates aluminum adjuvant activity
Thomas Marichal,Keiichi Ohata,Denis Bedoret,Claire Mesnil,Catherine Sabatel,Kouji Kobiyama,Pierre Lekeux,Cevayir Coban,Shizuo Akira,Ken Ishii,Fabrice Bureau,Christophe Desmet +11 more
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TLDR
The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase the understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.Abstract:
Aluminum-based adjuvants (aluminum salts or alum) are widely used in human vaccination, although their mechanisms of action are poorly understood. Here we report that, in mice, alum causes cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity. Furthermore, we propose that host DNA signaling differentially regulates IgE and IgG1 production after alum-adjuvanted immunization. We suggest that, on the one hand, host DNA induces primary B cell responses, including IgG1 production, through interferon response factor 3 (Irf3)-independent mechanisms. On the other hand, we suggest that host DNA also stimulates 'canonical' T helper type 2 (T H 2) responses, associated with IgE isotype switching and peripheral effector responses, through Irf3-dependent mechanisms. The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase our understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.read more
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STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors
Liufu Deng,Hua Liang,Meng Xu,Xuanming Yang,Byron Burnette,Ainhoa Arina,Xiao Dong Li,Helena J. Mauceri,Michael A. Beckett,Thomas E. Darga,Xiaona Huang,Thomas F. Gajewski,Zhijian J. Chen,Yang Xin Fu,Ralph R. Weichselbaum +14 more
TL;DR: Radiation-mediated antitumor immunity in immunogenic tumors requires a functional cytosolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve radiotherapy.
Journal ArticleDOI
STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors
Seng Ryong Woo,Mercedes Beatriz Fuertes,Leticia Corrales,Stefani Spranger,Michael J. Furdyna,Michael Y. K. Leung,Ryan Duggan,Ying Wang,Glen N. Barber,Katherine A. Fitzgerald,Maria-Luisa Alegre,Thomas F. Gajewski +11 more
TL;DR: It is found that spontaneous CD8(+) T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway.
Journal ArticleDOI
Key roles of adjuvants in modern vaccines
TL;DR: The potential benefits and importance of formulation and mechanisms of action of adjuvants are outlined and safety considerations are emphasized in the clinical development of effective adjuvant that will help facilitate effective next-generation vaccines against devastating infectious diseases.
Journal ArticleDOI
Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects
TL;DR: Cells from cGAS-deficient mice, including fibroblasts, macrophages, and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection, and were more susceptible to lethal infection with herpes simplex virus 1 than wild-type mice.
References
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Journal ArticleDOI
Genomic DNA Released by Dying Cells Induces the Maturation of APCs
Ken Ishii,Koichi Suzuki,Cevayir Coban,Fumihiko Takeshita,Yasushi Itoh,Hana Matoba,Leonard D. Kohn,Dennis M. Klinman +7 more
TL;DR: The maturation of APC induced by dsDNA may promote host survival by improving immune surveillance at sites of tissue injury/infection.
Journal ArticleDOI
Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies.
Tohru Kimura,Yuzo Kadokawa,Hisashi Harada,Hisashi Harada,Masahito Matsumoto,Masahito Matsumoto,Mitsuharu Sato,Mitsuharu Sato,Yasuo Kashiwazaki,Masahito Tarutani,Rosemary Sok-Pin Tan,Rosemary Sok-Pin Tan,Tomohiro Takasugi,Tomohiro Takasugi,Toshifumi Matsuyama,Tak W. Mak,Shigeru Noguchi,Tadatsugu Taniguchi,Tadatsugu Taniguchi +18 more
TL;DR: This work has shown that the stimulation of receptors by an IFN responsive element results in the induction of downstream target genes, and the ISRE sequence overlaps with that ofIRF‐E which binds another IFN‐inducible factor, IRF‐1 (IFN regulatory factor‐1).
Journal Article
Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation.
TL;DR: Findings demonstrate that in the early phase of the immune response, aluminium hydroxide exerts its regulatory effect at the level of the antigen-presenting and mediator-releasing accessory cell.
Journal ArticleDOI
Dendritic cells and monocyte/macrophages that create the IL-6/APRIL-rich lymph node microenvironments where plasmablasts mature
Elodie Mohr,Karine Serre,Rudolf A. Manz,Adam F. Cunningham,Mahmood Khan,Debbie L. Hardie,Roger Bird,Ian C. M. MacLennan +7 more
TL;DR: Two subsets of myeloid cells that associate with the AFC and are the main producers of these factors during a T-dependent Ab response to alum-precipitated protein in mouse lymph nodes are identified.
Journal ArticleDOI
Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties
Norihisa Goto,Hiroshi Kato,Jun-ichi Maeyama,Michiko Shibano,Takuya Saito,Junji Yamaguchi,Shinobu Yoshihara +6 more
TL;DR: Results suggest that calcium phosphate adjuvant may not be an useful alternative to Al adjUvant.