Steinfelder Svenja, Andersen John F, Cannons Jennifer L, Feng Carl G, Joshi Manju, Dwyer Dennis, Caspar Pat, Schwartzberg Pamela L, Sher Alan, Jankovic Dragana
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Exp Med. 2009 Aug 3;206(8):1681-90. doi: 10.1084/jem.20082462. Epub 2009 Jul 27.
Schistosoma mansoni eggs contain factors that trigger potent Th2 responses in vivo and condition mouse dendritic cells (DCs) to promote Th2 lymphocyte differentiation. Using an in vitro bystander polarization assay as the readout, we purified and identified the major Th2-inducing component from soluble egg extract (SEA) as the secreted T2 ribonuclease, omega-1. The Th2-promoting activity of omega-1 was found to be sensitive to ribonuclease inhibition and did not require MyD88/TRIF signaling in DCs. In common with unfractioned SEA, the purified native protein suppresses lipopolysaccharide-induced DC activation, but unlike SEA, it fails to trigger interleukin 4 production from basophils. Importantly, omega-1-exposed DCs displayed pronounced cytoskeletal changes and exhibited decreased antigen-dependent conjugate formation with CD4(+) T cells. Based on this evidence, we hypothesize that S. mansoni omega-1 acts by limiting the interaction of DCs with CD4(+) T lymphocytes, thereby lowering the strength of the activation signal delivered.
曼氏血吸虫卵含有能在体内引发强烈Th2反应的因子，并使小鼠树突状细胞（DCs）处于特定状态以促进Th2淋巴细胞分化。我们以体外旁观者极化分析作为检测指标，从可溶性虫卵提取物（SEA）中纯化并鉴定出主要的Th2诱导成分，即分泌型T2核糖核酸酶ω-1。结果发现，ω-1的Th2促进活性对核糖核酸酶抑制敏感，且在DCs中不需要MyD88/TRIF信号传导。与未分级的SEA一样，纯化的天然蛋白可抑制脂多糖诱导的DC激活，但与SEA不同的是，它不能触发嗜碱性粒细胞产生白细胞介素4。重要的是，暴露于ω-1的DCs表现出明显的细胞骨架变化，并且与CD4(+) T细胞形成的抗原依赖性共轭物减少。基于这些证据，我们推测曼氏血吸虫ω-1通过限制DCs与CD4(+) T淋巴细胞的相互作用来发挥作用，从而降低传递的激活信号强度。
