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Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type

机译:氢氧化铝佐剂诱导巨噬细胞向特定的抗原呈递细胞类型分化

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摘要

Aluminum hydroxide (AlOOH) has been used for many years as a vaccine adjuvant, but little is known about its mechanism of action. We investigated in this study the in vitro effect of aluminum hydroxide adjuvant on isolated macrophages. We showed that AlOOH-stimulated macrophages contain large and persistent intracellular crystalline inclusions, a characteristic property of muscle infiltrated macrophages described in animal models of vaccine injection, as well as in the recently described macrophagic myofasciitis (MMF) histological reaction in humans. AlOOH-loaded macrophages exhibited phenotypical and functional modifications, as they expressed the classical markers of myeloid dendritic cells (HLA-DRhigh/CD86(high)/CD83(+)/CD1a(-)/CD14(-)) and displayed potent ability to induce MHC-II-restricted antigen specific memory responses, but kept a macrophage morphology. This suggests a key role of macrophages, in the reaction to AlOOH-adjuvanted vaccines and these mature antigen-presenting macrophages may therefore be of particular importance in the establishment of memory responses and in vaccination mechanisms leading to long-lasting protection.
机译:氢氧化铝(AlOOH)已被用作疫苗佐剂多年,但对其作用机理知之甚少。在这项研究中,我们研究了氢氧化铝佐剂对离体巨噬细胞的体外作用。我们显示,AlOOH刺激的巨噬细胞包含大量且持久的细胞内晶体包涵体,这是在疫苗注射的动物模型以及最近描述的人类巨噬性肌筋膜炎(MMF)组织学反应中描述的肌肉浸润巨噬细胞的特征。载有AlOOH的巨噬细胞表现出表型和功能性修饰,因为它们表达了髓样树突状细胞的经典标记(HLA-DRhigh / CD86(high)/ CD83(+)/ CD1a(-)/ CD14(-)),并显示了强大的能力诱导MHC-II限制性抗原特异性记忆反应,但保持巨噬细胞形态。这表明巨噬细胞在与AlOOH佐剂疫苗反应中的关键作用,因此这些成熟的呈递抗原的巨噬细胞在建立记忆应答和导致长期保护的疫苗接种机制中可能特别重要。

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