Sticholysins (Sts) I and II (StI and StII) are pore-forming proteins (PFPs), purified from the Caribbean Sea anemone Stichodactyla helianthus. StII encapsulated into liposomes induces a robust antigen-specific cytotoxic CD8⁺ T lymphocytes (CTL) response and in its free form the maturation of bone marrow-derived dendritic cells (BM-DCs). It is probable that the latter is partially supporting in part the immunomodulatory effect on the CTL response induced by StII-containing liposomes. In the present work, we demonstrate that the StII’s ability of inducing maturation of BM-DCs is also shared by StI, an isoform of StII. Using heat-denatured Sts we observed a significant reduction in the up-regulation of maturation markers indicating that both PFP’s ability to promote maturation of BM-DCs is dependent on their conformational characteristics. StII-mediated DC maturation was abrogated in BM-DCs from toll-like receptor (TLR) 4 and myeloid differentiation primary response gene 88 (MyD88)-knockout mice but not in cells from TLR2-knockout mice. Furthermore, the antigen-specific CTL response induced by StII-containing liposomes was reduced in TLR4-knockout mice. These results indicate that StII, and probably by extension StI, has the ability to induce maturation of DCs through a TLR4/MyD88-dependent pathway, and that this activation contributes to the CTL response generated by StII-containing liposomes.

Sticholysins（Sts）I和II（StI和StII）是成孔蛋白（PFP），是从加勒比海海葵Stichodactyla helianthus中纯化得到的。包裹在脂质体中的StII诱导产生强大的抗原特异性细胞毒性CD8 ⁺T淋巴细胞（CTL）的反应及其游离形式的成熟骨髓衍生树突状细胞（BM-DCs）。后者可能部分地支持了对由含StII的脂质体诱导的CTL反应的免疫调节作用。在目前的工作中，我们证明了StII诱导BM-DCs成熟的能力也被StI（StII的同工型）所共有。使用热变性的Sts，我们观察到成熟标记的上调显着减少，表明PFP促进BM-DC成熟的能力取决于它们的构象特征。StII介导的DC成熟从收费样受体（TLR）4和骨髓分化主要反应基因88（MyD88）敲除小鼠的BM-DC中被废除，而在TLR2敲除小鼠的细胞中则被废除。此外，TLR4基因敲除小鼠减少了由含StII的脂质体诱导的抗原特异性CTL反应。这些结果表明，StII，并可能通过扩展StI，具有通过TLR4 / MyD88依赖性途径诱导DC成熟的能力，并且这种激活有助于由含StII的脂质体产生的CTL反应。