Immunomodulation by IPSE/alpha-1, an excretory/secretory protein from Schistosoma mansoni eggs

慢性血吸虫病的特征是由寄生虫卵引起的强烈抗炎免疫反应。我们先前已经鉴定了一种可触发嗜碱性粒细胞释放IL-4和IL-13的卵蛋白产物IPSE/α-1。值得注意的是，这些细胞因子通过减少促炎细胞因子释放和通过诱导抗炎的交替激活的巨噬细胞（AAM）来抑制炎症。由于嗜碱性粒细胞迁移到寄生虫感染的组织，并参与诱导AAM，我们提出，通过触发嗜碱性粒细胞IL-4 IPSE/α-1下调炎症过程。我们实验室未发表的数据支持这一假设。有趣的是，IPSE/α-1激活的嗜碱性粒细胞的抗炎作用被TLR配体放大。我们计划系统地研究IPSE/alpha-1的影响：i）对细胞共培养系统中促炎/抗炎细胞因子释放的影响，ii）对嗜碱性粒细胞以外的免疫细胞的影响，包括介质释放和功能性后果，iii）对慢性实验性结肠炎的保护作用。我们希望我们的研究将有助于开发治疗慢性炎症如过敏和自身免疫性疾病的新策略。

Chronic schistosomiasis is characterized by a strong anti-inflammatory immune response caused by schistosome eggs. We have earlier identified a schistosome egg product, IPSE/alpha-1, that triggers basophils to release IL-4 and IL-13. Notably, these cytokines inhibit inflammation by re-ducing pro-inflammatory cytokine release and by inducing anti-inflammatory alternatively activated macrophages (AAMs). Since basophils migrate to parasite-affected tissues and are involved in inducing AAMs, we propose that by triggering basophil IL-4 IPSE/alpha-1 turns down inflammatory processes. Unpublished data from our lab support this hypothesis. Interestingly, the anti-inflammatory effect of IPSE/alpha-1-activated basophils is amplified by TLR ligands. We plan to systematically investigate the effects of IPSE/alpha-1: i) on pro-/anti-inflammatory cytokine release in cell co-culture systems, ii) on immune cells beyond basophils including mediator release and functional consequen-ces, and iii) regarding protection against chronic experimental colitis. We expect our study will help develop new strategies for treating chronic inflammations such as allergy and autoimmune diseases.