Modulation of soluble and particulate antigen transport in afferent lymph by monophosphoryl lipid A
Modulation of soluble and particulate antigen transport in afferent lymph by monophosphoryl lipid A
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DOI：
10.1038/icb.2011.53
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发表时间：
2012-04-01
影响因子：
4
通讯作者：
Meeusen, Els N. T.
中科院分区：
文献类型：
--
作者：
de Veer, Michael;Kemp, Joanna;Meeusen, Els N. T.
疫苗佐剂刺激先天免疫系统，并决定诱导免疫反应的结果。因此，更好地了解它们的行动对于开发新的更安全的疫苗至关重要。单磷酰脂A(MPL)是一种脱毒的脂多糖，是人类疫苗中一种很有前途的新型佐剂成分。本研究使用绵羊淋巴管模型来研究细胞募集和抗原从注射部位到传入淋巴的运输，以及联合注射MPL是如何调节这一过程的。与生理盐水相比，注射MPL仅引起淋巴流量的微小变化，并且在迁移到淋巴中的细胞数量上没有差异。然而，在最初的12小时内，MPL确实引起中性粒细胞和单核细胞的募集显著增加，但树突状细胞(DC)并不进入淋巴。可溶性卵蛋白(OVA)抗原在24小时内自由流入淋巴，在注射MPL的6-9小时略有减少。卵子包裹的荧光1-mU珠子最初主要由中性粒细胞转运，24-72小时由DC转运。MPL诱导中性粒细胞和单核细胞对珠子的运输增加和更持久，尽管它不增加这些细胞的吞噬能力。与铝佐剂相比，MPL在后期并不增加DC对珠子的转运。这些研究为不同佐剂在体内的作用以及疫苗接种后建立免疫反应的初始事件提供了重要的新见解。《免疫学和细胞生物学》(2012年)90404410；doi：10.1038/icb.2011.53；2011年6月7日在线发布
Vaccine adjuvants stimulate the innate immune system and determine the outcome of the immune response induced. A better understanding of their action is therefore crucial to the development of new and safer vaccines. Monophosphoryl lipid A (MPL), a 'detoxified' version of lipolysaccharide, is a promising new adjuvant component in human vaccines. The present study uses an ovine lymphatic cannulation model to study cell recruitment and antigen transport from the injection site into the afferent lymph, and how this is modulated by co-injection with MPL. Compared with saline, MPL injections caused only minor variations in lymph flow and no difference in cell number migrating into the lymph. MPL did, however, cause a significantly increased recruitment of neutrophils and monocytes, but not dendritic cells (DC) into the lymph for the first 12 h. Soluble ovalbumin (OVA) antigen flowed freely into the lymph over a 24-h period and was slightly reduced at 6-9 h in the MPL-injected sites. OVA-coated fluorescent 1-mu beads were initially transported predominantly by neutrophils and, from 24 to 72 h, by DC. MPL induced an increased and more sustained transport of beads by neutrophils and monocytes although it did not increase the phagocytic capacity of these cells. In contrast to aluminium adjuvant, MPL did not increase bead transport by DC at the later time point. These studies provide important new insights in the in vivo action of different adjuvants and the initial events that set up an immune response after vaccination. Immunology and Cell Biology (2012) 90, 404-410; doi:10.1038/icb.2011.53; published online 7 June 2011