Synthetic mycobacterial molecular patterns partially complete Freund's adjuvant
Synthetic mycobacterial molecular patterns partially complete Freund's adjuvant
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DOI：
10.1038/s41598-020-62543-5
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发表时间：
2020-04-03
影响因子：
4.6
通讯作者：
Behr, Marcel A.
中科院分区：
文献类型：
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作者：
Dube, Jean-Yves;McIntosh, Fiona;Behr, Marcel A.
完全弗氏佐剂（CFA）历来是免疫学家最有用的工具之一。基本上由死亡的分枝杆菌和矿物油组成，我们问自己这种佐剂的分枝杆菌部分有什么特别之处，它能被合成吗？在这里，我们证明了N-羟乙酰化肽聚糖加上海藻糖二霉菌酸酯（两者在分枝杆菌中都是独特的）对于使用敲除和化学互补的完全佐剂效应的重要性。合成的N-羟乙酰胞壁酰二肽和最小海藻糖二霉菌酸酯基序GlcC 14 C18的组合能够上调树突状细胞效应器，并且诱导实验性自身免疫，与CFA相比，在质量上相似，但在数量上更温和。这项研究概述了如何用一种一致的、分子定义的佐剂替代CFA，这可能会为从细胞介导的免疫中受益的免疫抑制剂和疫苗的设计提供信息。我们还期望使用合成的微生物相关分子模式（MAMPs）来研究分枝杆菌免疫和免疫发病机制。
Complete Freund's adjuvant (CFA) has historically been one of the most useful tools of immunologists. Essentially comprised of dead mycobacteria and mineral oil, we asked ourselves what is special about the mycobacterial part of this adjuvant, and could it be recapitulated synthetically? Here, we demonstrate the essentiality of N-glycolylated peptidoglycan plus trehalose dimycolate (both unique in mycobacteria) for the complete adjuvant effect using knockouts and chemical complementation. A combination of synthetic N-glycolyl muramyl dipeptide and minimal trehalose dimycolate motif GlcC14C18 was able to upregulate dendritic cell effectors, plus induce experimental autoimmunity qualitatively similar but quantitatively milder compared to CFA. This research outlines how to substitute CFA with a consistent, molecularly-defined adjuvant which may inform the design of immunotherapeutic agents and vaccines benefitting from cell-mediated immunity. We also anticipate using synthetic microbe-associated molecular patterns (MAMPs) to study mycobacterial immunity and immunopathogenesis.