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Abstract Title:

DNA released from dying host cells mediates aluminum adjuvant activity.

Abstract Source:

Nat Med. 2011 Aug ;17(8):996-1002. Epub 2011 Jul 17. PMID: 21765404

Abstract Author(s):

Thomas Marichal, Keiichi Ohata, Denis Bedoret, Claire Mesnil, Catherine Sabatel, Kouji Kobiyama, Pierre Lekeux, Cevayir Coban, Shizuo Akira, Ken J Ishii, Fabrice Bureau, Christophe J Desmet

Article Affiliation:

Thomas Marichal

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.

Study Type : Animal Study

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Sayer Ji
Founder of GreenMedInfo.com

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