Alum Induces Innate Immune Responses through Macrophage and Mast Cell Sensors, But These Sensors Are Not Required for Alum to Act As an Adjuvant for Specific Immunity

被引:301
作者
McKee, Amy S. [2 ]
Munks, Michael W. [2 ]
MacLeod, Megan K. L. [2 ]
Fleenor, Courtney J. [5 ]
Van Rooijen, Nico [3 ]
Kappler, John W. [2 ,4 ]
Marrack, Philippa [1 ,2 ,5 ]
机构
[1] Natl Jewish Ctr Immunol & Resp Med, Howard Hughes Med Inst, Dept Immunol, Denver, CO 80206 USA
[2] Natl Jewish Hlth, Integrated Dept Immunol, Denver, CO 80206 USA
[3] Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, Amsterdam, Netherlands
[4] Univ Colorado, Hlth Sci Ctr, Program Biomol Struct, Aurora, CO 80045 USA
[5] Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
关键词
INFLAMMATORY DENDRITIC CELLS; ANTIGEN-PRESENTING CELLS; TOLL-LIKE RECEPTORS; T-CELLS; NALP3; INFLAMMASOME; IN-VIVO; IL-4; PRODUCTION; ANTIBODY-RESPONSES; URIC-ACID; ACTIVATION;
D O I
10.4049/jimmunol.0900164
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 It of injection including IL-1 beta and IL-5. Optimal production of some of these, including IL-1 beta, 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-1 beta. 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 Journal of Immunology, 2009, 183: 4403-4414.
引用
收藏
页码:4403 / 4414
页数:12
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