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,¶
* Howard Hughes Medical Institute and
Integrated Department of Immunology, National Jewish Health, Denver, CO 80206;
Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands;
Program in Biomolecular Structure, and
¶ Department of Biochemistry and Molecular Genetics, University of Colorado Health Science Center, Aurora, CO 80045
To understand more about how the body recognizes alum we characterized the early innate and adaptive responses in mice injected with the adjuvant. Within hours of exposure, alum induces a type 2 innate response characterized by an influx of eosinophils, monocytes, neutrophils, DCs, NK cells and NKT cells. In addition, at least 13 cytokines and chemokines are produced within 4 h of injection including IL-1β and IL-5. Optimal production of some of these, including IL-1β, depends upon both macrophages and mast cells, whereas production of others, such as IL-5, depends on mast cells only, suggesting that both of these cell types can detect alum. Alum induces eosinophil accumulation partly through the production of mast cell derived IL-5 and histamine. Alum greatly enhances priming of endogenous CD4 and CD8 T cells independently of mast cells, macrophages, and of eosinophils. In addition, Ab levels and Th2 bias was similar in the absence of these cells. We found that the inflammation induced by alum was unchanged in caspase-1-deficient mice, which cannot produce IL-1β. Furthermore, endogenous CD4 and CD8 T cell responses, Ab responses and the Th2 bias were also not impacted by the absence of caspase-1 or NLRP3. These data suggest that activation of the inflammasome and the type 2 innate response orchestrated by macrophages and mast cells in vivo are not required for adjuvant effect of alum on endogenous T and B cell responses.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by U.S. Public Health Service Grants AI-18785, AI-52225, and AI 22295.
2 Address correspondence and reprint requests Dr. Philippa Marrack, Department of Immunology, Howard Hughes Medical Institute, 1400 Jackson Street, Denver, CO 80206. E-mail address: marrackp{at}njc.org
3 Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; MIG, monokine-induced by 
-IFN; IP-10, 10-kDa IFN-induced protein; KC, keratinocyte-derived chemokine; WT, wild type.
4 The online version of this article contains supplemental material.
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