Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes
Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes
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DOI：
10.1016/j.vaccine.2010.12.090
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发表时间：
2011-02-17
期刊：
影响因子：
5.5
通讯作者：
Wack, Andreas
中科院分区：
文献类型：
--
作者：
Calabro, Samuele;Tortoli, Marco;Wack, Andreas
疫苗佐剂如明矾和水包油乳剂MF 59用于增强对纯可溶性抗原的免疫应答，但它们的作用机制在很大程度上仍不清楚。由于大多数含佐剂的疫苗都是肌内注射，我们研究了小鼠肌肉中的免疫反应，发现两种佐剂都是趋化因子产生的有效诱导剂，并促进了CD11b（+）细胞的快速募集。最早和最丰富的募集细胞类型是中性粒细胞，其次是单核细胞，嗜酸性粒细胞和后来的树突状细胞（DC）和巨噬细胞。使用荧光形式的MF59和卵清蛋白（OVA）抗原，我们表明，所有招募的细胞类型采取的佐剂和抗原运输到引流淋巴结（LN）。在那里，我们在注射后数小时内发现了抗原阳性中性粒细胞和单核细胞，随后是B细胞和DC。与明矾相比，MF 59注射导致更显著的中性粒细胞募集和更有效的抗原从注射部位重新定位到LN。由于在引流淋巴结中观察到抗原转运中性粒细胞，我们询问这些细胞是否在MF59介导的佐剂性中发挥重要作用。然而，抗体介导的中性粒细胞消融使MF59的佐剂性不变。进一步的研究将揭示其他单细胞类型是否至关重要，或者不同的招募细胞群是否具有重叠的功能。(C)2010爱思唯尔有限公司版权所有。
Vaccine adjuvants such as alum and the oil-in-water emulsion MF59 are used to enhance immune responses towards pure soluble antigens, but their mechanism of action is still largely unclear. Since most adjuvanted vaccines are administered intramuscularly, we studied immune responses in the mouse muscle and found that both adjuvants were potent inducers of chemokine production and promoted rapid recruitment of CD11b(+) cells. The earliest and most abundantly recruited cell type are neutrophils, followed by monocytes, eosinophils and later dendritic cells (DCs) and macrophages. Using fluorescent forms of MF59 and ovalbumin (OVA) antigen, we show that all recruited cell types take up both adjuvant and antigen to transport them to the draining lymph nodes (LNs). There, we found antigen-positive neutrophils and monocytes within hours of injection, later followed by B cells and DCs. Compared to alum, MF59-injection lead to a more prominent neutrophil recruitment and a more efficient antigen re-localization from the injection site to the LN. As antigen-transporting neutrophils were observed in draining LNs, we asked whether these cells play an essential role in MF59-mediated adjuvanticity. However, antibody-mediated neutrophil ablation left MF59-adjuvanticity unaltered. Further studies will reveal whether other single cell types are crucial or whether the different recruited cell populations are redundant with overlapping functions. (C) 2010 Elsevier Ltd. All rights reserved.