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.
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.
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DOI：
10.4049/jimmunol.0900164
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发表时间：
2009-10-01
期刊：
影响因子：
--
通讯作者：
Marrack P
中科院分区：
文献类型：
--
作者：
McKee AS;Munks MW;MacLeod MK;Fleenor CJ;Van Rooijen N;Kappler JW;Marrack P
为了更好地了解身体如何识别明矾，我们对注射佐剂的小鼠的早期先天和适应性反应进行了表征。接触明矾数小时后，明矾诱发2型先天反应，其特征是嗜酸性粒细胞、单核细胞、中性粒细胞、dc、NK细胞和NKT细胞大量涌入。此外，至少有13种细胞因子和趋化因子在注射后4小时内产生，包括IL-1β和IL-5。其中一些的最佳生产，包括IL-1β，取决于巨噬细胞和肥大细胞，而其他的生产，如IL-5，仅取决于肥大细胞，这表明这两种细胞类型都可以检测明矾。明矾通过产生肥大细胞源性IL-5和组胺诱导嗜酸性粒细胞积累。明矾极大地增强了内源性CD4和CD8 T细胞的启动，而不依赖于肥大细胞、巨噬细胞和嗜酸性粒细胞。此外，在没有这些细胞的情况下，抗体水平和Th2偏倚相似。我们发现明矾引起的炎症在caspase-1缺陷小鼠中没有改变，caspase-1缺陷小鼠不能产生IL-1β。此外，内源性CD4和CD8 T细胞反应、抗体反应和Th2偏倚也不受caspase-1或NLRP3缺失的影响。这些数据表明，明铝对内源性T细胞和B细胞反应的辅助作用并不需要激活炎性体和巨噬细胞和肥大细胞在体内精心策划的2型先天反应。
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 thirteen cytokines and chemokines are produced within 4 hours of injection including IL-1β and IL-5. Optimal production of some of these, including IL-1β, depends upon both macrophages and mast cells, while 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, antibody 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, antibody 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 alum's adjuvant effects on endogenous T and B cell responses.
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DOI：
10.1084/jem.192.5.741
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsuda JL;Naidenko OV;Gapin L;Nakayama T;Taniguchi M;Wang CR;Koezuka Y;Kronenberg M
通讯作者：
Kronenberg M
影响因子：
4.4
作者：
Li, Hanfen;Willingham, Stephen B.;Ting, Jenny P. -Y.;Re, Fabio
通讯作者：
Re, Fabio
影响因子：
32.4
作者：
Kopf, M;Brombacher, F;Matthaei, KI
通讯作者：
Matthaei, KI
影响因子：
5.5
作者：
McDonald, Fiona;Mohrs, Markus;Brewer, James
通讯作者：
Brewer, James
DOI：
10.1073/pnas.0807449105
发表时间：
2008-09-23
影响因子：
11.1
作者：
MacLeod, Megan K. L.;McKee, Amy;Marrack, Philippa
通讯作者：
Marrack, Philippa