Thioredoxin peroxidase secreted by Fasciola hepatica induces the alternative activation of macrophages
Thioredoxin peroxidase secreted by Fasciola hepatica induces the alternative activation of macrophages
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DOI：
10.1128/iai.73.1.166-173.2005
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Dalton, JP
中科院分区：
文献类型：
--
作者：
Donnelly, S;O'Neill, SM;Dalton, JP
替代活化的巨噬细胞（AAMphi）主要与寄生虫感染的慢性阶段和极化Th 2应答的发展相关。我们已经表明，肝片吸虫感染的BALB/c小鼠诱导极化的Th 2反应在潜伏期和慢性期的疾病。通过评估替代活化的遗传标记物，即Fizz 1、Ym 1和Arg 1的表达，在蠕虫感染的该模型中分析巨噬细胞的活化状态。AAMphi在F.肝感染和腹腔注射寄生虫排泄分泌（ES）产物后。管理的重组抗氧化剂硫氧还蛋白过氧化物酶（TPx），这是包含在ES产品，也诱导AAMphi的招聘到腹膜。体外研究表明，这种重组TPx直接将RAW 264.7巨噬细胞转化为替代活化表型，其特征在于产生高水平的白细胞介素-10（IL-10）、前列腺素E-2，对应于低水平的IL-12。我们的数据表明，蠕虫F.肝巨噬细胞的增殖是通过分泌分子介导的，其中一种是TPx，其诱导巨噬细胞的募集和交替激活。
Alternatively activated macrophages (AAMphi) are primarily associated with the chronic stages of parasitic infections and the development of a polarized Th2 response. We have shown that Fasciola hepatica infection of BALB/c mice induces a polarized Th2 response during both the latent and chronic stage of disease. The activation status of macrophages was analyzed in this model of helminth infection by evaluating the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arg1. AAMphi were recruited to the peritoneum of mice within 24 h of F. hepatica infection and after intraperitoneal injection of parasite excretory-secretory (ES) products. Administration of a recombinant antioxidant thioredoxin peroxidase (TPx), which is contained within the ES products, also induced the recruitment of AAMphi to the peritoneum. In vitro studies showed that this recombinant TPx directly converts RAW 264.7 macrophages to an alternatively activated phenotype characterized by the production of high levels of interleukin-10 (IL-10), prostaglandin E-2, corresponding with low levels of IL-12. Our data suggest that the Th2 responses induced by the helminth F. hepatica are mediated through the secretion of molecules, one of which is TPx, that induce the recruitment and alternative activation of macrophages.