[en] Aluminum-based adjuvants (alum) are widely used in human vaccination, although little is understood of their mechanisms of action. Here, we report that, in mice, alum causes the 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 upon alum immunization. Indeed, we support that host DNA induces primary B cell responses, including IgG1 production, through Interferon Response Factor (Irf) 3-independent mechanisms, and 'canonical' type 2 T cell responses associated with IgE isotype switching and peripheral effector responses through Irf3-dependent mechanisms. The finding that host cell DNA is a damage-associated molecular pattern relaying alum adjuvant activity may thus help in the comprehension of the mechanisms of action of current vaccines and in the design of novel adjuvants.
Research Center/Unit :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Marichal, Thomas ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Ohata, Keiichi; University of Osaka
Bedoret, Denis
Mesnil, Claire ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Sabatel, Catherine ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Kobiyama, Kouji; University of Osaka
Lekeux, Pierre ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie
Coban, Cevayir; University of Osaka
Akira, Shizuo; University of Osaka
Ishii, Ken J; University of Osaka
Bureau, Fabrice ✱; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Desmet, Christophe ✱; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
✱ These authors have contributed equally to this work.
Language :
English
Title :
DNA released from dying host cells mediates aluminum adjuvant activity
Publication date :
August 2011
Journal title :
Nature Medicine
ISSN :
1078-8956
eISSN :
1546-170X
Publisher :
Nature Publishing Group, New York, United States - New York
F.R.S.-FNRS - Fonds de la Recherche Scientifique FRSM - Fonds de la Recherche Scientifique Médicale PAI Grant-in-Aid for Scientific Research of the Japanese Ministry of Education, Culture, Sport, Science and Technology Core Research Evolutionary Science and Technology (CREST) program at the Japan Science and Technology Agency
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