School of Veterinary Medicine & Science, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, UK.
Vet Res. 2011 Jun 27;42(1):80. doi: 10.1186/1297-9716-42-80.
Alternatively activated macrophages (AAM) are a key feature Th2 immunity and have been associated with a variety of roles during helminth infection. The role this cell subset plays in protozoan infection remain relatively unexplored, herein we describe the effects of a redox enzyme (rTgPrx) derived from Toxoplasma gondii on murine macrophage phenotype in vitro. RTgPrx has been previously associated with the maintainance of parasite oxidative balance. Here our experiments show that rTgPrx promotes AAM as indicated by high arginase-1 (arg-1), YM1 and FIZZ expression via both signal transducer and activator of transcription (STAT)6-dependent and -independent mechanisms. Additionally rTgPrx treatment reduced caspase-1 activity and IL-1β secretion, while simultaneously increasing IL-10 release. Furthermore the in vitro replication of T. gondii (RH strain) was enhanced when macrophages were treated with rTgPrx. This is in contrast with the previously described effects of a Plasmodium berghei ANKA 2-cys-peroxiredoxin that promotes pro-inflammatory cytokine production. These results highlight the role of T. gondii derived redox enzymes as important immune modulators and potentially indicate a role for AAM in modulating immunopathology and promoting parasite replication during T. gondii infection.
alternatively activated macrophages (AAM) 是 Th2 免疫的一个关键特征，与寄生虫感染过程中的各种角色有关。该细胞亚群在原生动物感染中的作用仍相对未知，在此，我们描述了来源于弓形虫的氧化还原酶 (rTgPrx) 对体外鼠巨噬细胞表型的影响。RTgPrx 先前与寄生虫氧化平衡的维持有关。在这里，我们的实验表明 rTgPrx 通过 STAT6 依赖性和非依赖性机制促进 AAM，表现为高精氨酸酶-1 (arg-1)、YM1 和 FIZZ 的表达。此外，rTgPrx 处理降低了半胱氨酸蛋白酶-1 的活性和 IL-1β 的分泌，同时增加了 IL-10 的释放。此外，当用 rTgPrx 处理巨噬细胞时，弓形虫 (RH 株) 的体外复制增加。这与先前描述的疟原虫伯氏疟原虫 2-cys-过氧化物酶促进促炎细胞因子产生的作用相反。这些结果强调了弓形虫来源的氧化还原酶作为重要免疫调节剂的作用，并可能表明 AAM 在调节免疫病理学和促进弓形虫感染期间寄生虫复制中的作用。
