已知常规抗原呈递涉及抗原的吞噬作用,随后其在胞吞区室中内化,并通过MHCII类分子呈递CD4T细胞的表位。然而,自1976年以来,已经研究了交叉呈递途径,其中CD8T细胞通过MHCI类被树突状细胞(DC)通过吞噬作用或内吞作用获得的抗原激活。在一些参与交叉呈递的重要分子中,Dectin-1簇(CLEC)的C型凝集素受体,特别是CLEC9A受体,不仅在树突状细胞中表达,而且在这种情况下也具有关键作用。在特别的,CLEC12A已被强调为疟疾色素疟原虫色素(HZ)受体。在疟原虫感染期间,嗜血色素晶体保护寄生虫免受红细胞内血红素毒性,以及释放的天然HZ引发促炎反应并可诱导交叉呈递。特别是,这种晶体可以从希马汀酸酐合成并模拟天然形式,并且在其合成过程中在纳米晶体域之间产生的间隙允许物质偶联,然后进行涂层。因此,这项研究旨在评估合成的疟原虫色素(sHz)或血红素酸酐是否可以成为纳米载体并促进树突状细胞的交叉呈递.首先,验证了sHz可以携带包被和偶联的抗原,这些化合物可以与LAMP1阳性囊泡缔合并降低细胞内的整体pH,这可能会增强卵清蛋白和婴儿利什曼原虫抗原的交叉呈递。因此,这项研究不仅显示了sHz免疫调节特性,而且显示了其作为抗原载体的潜在应用,为抗原呈递的分子复杂性增加了重要数据。
It is known that conventional antigen presentation involves phagocytosis of antigens followed by its internalization in endocytic compartments and presentation of epitopes through MHC class II molecules for CD4 T cells. However, since 1976 a cross-presentation pathway has been studied, in which CD8 T cells are activated via MHC class I with antigens acquired through phagocytosis or endocytosis by dendritic cells (DCs). Among some important molecules involved in the cross-presentation, the C-type lectin receptor of the Dectin-1 cluster (CLECs), particularly the CLEC9A receptor, not only is expressed in dendritic cells but also presents a pivotal role in this context. In special, CLEC12A has been highlighted as a malaria pigment hemozoin (HZ) receptor. During Plasmodium infection, hemozoin crystals defend the parasite against heme toxicity within erythrocytes, as well as the released native HZ elicits pro-inflammatory responses and can induce cross-presentation. Particularly, this crystal can be synthesized from hematin anhydride and mimics the native form, and the gaps generated between the nanocrystal domains during its synthesis allow for substance coupling followed by its coating. Therefore, this study aimed to assess whether synthetic hemozoin (sHz) or hematin anhydride could be a nanocarrier and promote cross-presentation in dendritic cells. Firstly, it was verified that sHz can carry coated and coupled antigens, the compounds can associate to LAMP1-positive vesicles and decrease overall intracellular pH, which can potentially enhance the cross-presentation of ovalbumin and Leishmania infantum antigens. Thus, this study adds important data in the molecular intricacies of antigen presentation by showing not only the sHz immunomodulatory properties but also its potential applications as an antigen carrier.