Schistosomal-Derived Lysophosphatidylcholine Are Involved in Eosinophil Activation and Recruitment through Toll-Like Receptor-2-Dependent Mechanisms
Schistosomal-Derived Lysophosphatidylcholine Are Involved in Eosinophil Activation and Recruitment through Toll-Like Receptor-2-Dependent Mechanisms
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DOI：
10.1086/656477
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发表时间：
2010-11-01
影响因子：
6.4
通讯作者：
Bozza, Patricia T.
中科院分区：
文献类型：
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作者：
Magalhaes, Kelly G.;Almeida, Patricia E.;Bozza, Patricia T.
寄生虫衍生的脂质可能在宿主-病原体相互作用和逃逸机制中发挥重要作用。在此，我们评估了曼氏血吸虫感染中Toll样受体（TLR）-2和嗜酸性粒细胞活化中的巨噬细胞衍生脂质的作用。与野生型动物相比，缺乏TLR 2的小鼠在S.曼氏感染。嗜酸性粒细胞积聚和嗜酸性粒细胞脂质体（脂滴）形成减少，至少部分是由于嗜酸性粒细胞趋化因子、白细胞介素（IL）-5和IL-13的产生减少所致。与野生型小鼠中的相应产生相比，注意到曼氏感染的TLR 2（-/-）小鼠中的相应产生。虽然在急性溶酶体感染期间（长达50天）没有观察到存活率的差异，但在感染的慢性期观察到与野生型小鼠的存活率相比，TLR 2（-/-）小鼠的存活率增加。血吸虫脂质提取物和血吸虫衍生的溶血磷脂酰胆碱（lyso-PC）体外刺激巨噬细胞诱导TLR 2依赖性NF-κ B活化和细胞因子产生。此外，在体内溶酶体lyso-PC管理诱导嗜酸性粒细胞的招聘和细胞因子的产生，在很大程度上依赖于TLR 2的机制。综上所述，我们的研究结果表明，在S.曼氏感染。此外，我们的研究结果表明，TLR 2依赖性炎症反应，细胞因子的产生，嗜酸性粒细胞的招聘和激活可能有助于在慢性感染阶段的发病机制和致死率。
Parasite-derived lipids may play important roles in host-pathogen interactions and escape mechanisms. Herein, we evaluated the role of schistosomal-derived lipids in Toll-like receptor (TLR)-2 and eosinophil activation in Schistosoma mansoni infection. Mice lacking TLR2 exhibited reduced liver eosinophilic granuloma, compared with that of wild-type animals, following S. mansoni infection. Decreased eosinophil accumulation and eosinophil lipid body (lipid droplet) formation, at least partially due to reduced production of eotaxin, interleukin (IL)-5, and IL-13 in S. mansoni-infected TLR2(-/-) mice, compared with the corresponding production in wild-type mice, was noted. Although no differences were observed in survival rates during the acute schistosomal infection (up to 50 days), increased survival of TLR2(-/-) mice, compared with survival of wild-type mice, was observed during the chronic phase of infection. Schistosomal lipid extract- and schistosomal-derived lysophosphatidylcholine (lyso-PC)-stimulated macrophages in vitro induced TLR2-dependent NF-kB activation and cytokine production. Furthermore, in vivo schistosomal lyso-PC administration induced eosinophil recruitment and cytokine production, in a mechanism largely dependent on TLR2. Taken together, our results suggest that schistosomal-derived lyso-PC may participate in cytokine production and eosinophil activation through a TLR2-dependent pathway in S. mansoni infection. Moreover, our results suggest that TLR2-dependent inflammatory reaction, cytokine production, and eosinophil recruitment and activation may contribute to the pathogenesis and lethality in the chronic phase of infection.