Donnelly Sheila, O'Neill Sandra M, Sekiya Mary, Mulcahy Grace, Dalton John P
Institute for the Biotechnology of Infectious Diseases, University of Technology Sydney, Westbourne St., Gore Hill, Sydney, NSW 2065, Australia.
Infect Immun. 2005 Jan;73(1):166-73. doi: 10.1128/IAI.73.1.166-173.2005.
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.
替代性活化巨噬细胞（AAMphi）主要与寄生虫感染的慢性阶段以及极化的Th2反应的发展相关。我们已经表明，肝片吸虫感染BALB/c小鼠在疾病的潜伏和慢性阶段均诱导极化的Th2反应。在这种蠕虫感染模型中，通过评估替代性活化的遗传标志物即Fizz1、Ym1和Arg1的表达来分析巨噬细胞的活化状态。在肝片吸虫感染后24小时内以及腹腔注射寄生虫排泄-分泌（ES）产物后，AAMphi被募集到小鼠腹膜。ES产物中含有的重组抗氧化硫氧还蛋白过氧化物酶（TPx）的给药也诱导AAMphi募集到腹膜。体外研究表明，这种重组TPx直接将RAW 264.7巨噬细胞转化为以高水平白细胞介素-10（IL-10）、前列腺素E2产生为特征的替代性活化表型，同时IL-12水平较低。我们的数据表明，蠕虫肝片吸虫诱导的Th2反应是通过分子分泌介导的，其中之一是TPx，它诱导巨噬细胞的募集和替代性活化。
