[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.
Giga-Infection, Immunity and Inflammation
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Fonds de la Recherche Scientifique Médicale - FRSM ; 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