DNA released from dying host cells mediates aluminum adjuvant activity
| Autor: | Catherine Sabatel, Cevayir Coban, Shizuo Akira, Keiichi Ohata, Pierre Lekeux, Ken Ishii, Thomas Marichal, Christophe Desmet, Denis Bedoret, Claire Mesnil, Kouji Kobiyama, Fabrice Bureau |
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| Rok vydání: | 2011 |
| Předmět: |
Programmed cell death
medicine.medical_treatment Enzyme-Linked Immunosorbent Assay Biology General Biochemistry Genetics and Molecular Biology Mice Th2 Cells Adjuvants Immunologic Interferon medicine Animals Deoxyribonuclease I Alum adjuvant B cell Glycoproteins Mice Knockout B-Lymphocytes Cell Death Effector RNA-Binding Proteins DNA General Medicine Immunoglobulin E Flow Cytometry Mice Inbred C57BL medicine.anatomical_structure Immunoglobulin class switching Spectrophotometry Immunoglobulin G Toll-Like Receptor 9 Immunology Alum Compounds IRF3 Adjuvant Signal Transduction medicine.drug |
| Zdroj: | Nature Medicine. 17:996-1002 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.2403 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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