Dendritic cell–specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a cellular receptor for delta inulin adjuvant

IF 3.2 4区 医学 Q3 CELL BIOLOGY Immunology & Cell Biology Pub Date : 2024-05-17 DOI:10.1111/imcb.12774
Erica L Stewart, Claudio Counoupas, Megan Steain, Caroline Ashley, Sibel Alca, Lauren Hartley-Tassell, Mark von Itzstein, Warwick J Britton, Nikolai Petrovsky, James A Triccas
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Abstract

Delta inulin, or Advax, is a polysaccharide vaccine adjuvant that significantly enhances vaccine-mediated immune responses against multiple pathogens and was recently licensed for use in the coronavirus disease 2019 (COVID-19) vaccine SpikoGen. Although Advax has proven effective as an immune adjuvant, its specific binding targets have not been characterized. In this report, we identify a cellular receptor for Advax recognition. In vitro uptake of Advax particles by macrophage cell lines was substantially greater than that of latex beads of comparable size, suggesting an active uptake mechanism by phagocytic cells. Using a lectin array, Advax particles were recognized by lectins specific for various carbohydrate structures including mannosyl, N-acetylgalactosamine and galactose moieties. Expression in nonphagocytic cells of dendritic cell–specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), a C-type lectin receptor, resulted in enhanced uptake of fluorescent Advax particles compared with mock-transfected cells. Advax uptake was reduced with the addition of ethylenediaminetetraacetic acid and mannan to cells, which are known inhibitors of DC-SIGN function. Finally, a specific blockade of DC-SIGN using a neutralizing antibody abrogated Advax uptake in DC-SIGN–expressing cells. Together, these results identify DC-SIGN as a putative receptor for Advax. Given the known immunomodulatory role of DC-SIGN, the findings described here have implications for the use of Advax adjuvants in humans and inform future mechanistic studies.

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树突状细胞特异性细胞间粘附分子-3-抓取非整合素(DC-SIGN)是δ菊粉佐剂的细胞受体。
Delta inulin 或 Advax 是一种多糖疫苗佐剂,可显著增强疫苗介导的针对多种病原体的免疫反应,最近被授权用于冠状病毒病 2019(COVID-19)疫苗 SpikoGen。尽管 Advax 已被证明是一种有效的免疫佐剂,但其特异性结合靶点尚未被确定。在本报告中,我们确定了一种用于识别 Advax 的细胞受体。巨噬细胞系对 Advax 粒子的体外摄取量大大高于大小相当的乳胶珠,这表明吞噬细胞具有主动摄取机制。利用凝集素阵列,Advax 颗粒可被针对各种碳水化合物结构(包括甘露糖基、N-乙酰半乳糖胺和半乳糖分子)的凝集素识别。与模拟转染细胞相比,在非吞噬细胞中表达树突状细胞特异性细胞间粘附分子-3-抓取非整合素(DC-SIGN)(一种 C 型凝集素受体)可增强荧光 Advax 粒子的吸收。在细胞中加入乙二胺四乙酸和甘露聚糖后,Advax 的摄取会减少,而这两种物质是已知的 DC-SIGN 功能抑制剂。最后,使用中和抗体对 DC-SIGN 进行特异性阻断,可减少表达 DC-SIGN 的细胞对 Advax 的吸收。这些结果共同确定了 DC-SIGN 是 Advax 的一种假定受体。鉴于DC-SIGN具有已知的免疫调节作用,本文所述的研究结果对Advax佐剂在人类中的应用具有重要意义,并为未来的机理研究提供了参考。
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来源期刊
Immunology & Cell Biology
Immunology & Cell Biology 医学-免疫学
CiteScore
7.50
自引率
2.50%
发文量
98
审稿时长
4-8 weeks
期刊介绍: The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.
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