Reactive oxygen species (ROS) that are induced upon pathogen infection plays an important role in host defence. The rickettsial pathogen Anaplasma phagocytophilum, which is primarily transmitted by Ixodes scapularis ticks in the United States, has evolved many strategies to escape ROS and survive in mammalian cells. However, little is known on the role of ROS in A. phagocytophilum infection in ticks. Our results show that A. phagocytophilum and hemin induce activation of l‐tryptophan pathway in tick cells. Xanthurenic acid (XA), a tryptophan metabolite, supports A. phagocytophilum growth in tick cells through inhibition of tryptophan dioxygenase (TDO) activity leading to reduced l‐kynurenine levels that subsequently affects build‐up of ROS. However, hemin supports A. phagocytophilum growth in tick cells by inducing TDO activity leading to increased l‐kynurenine levels and ROS production. Our data reveal that XA and kynurenic acid (KA) chelate hemin. Furthermore, treatment of tick cells with 3‐hydroxyl l‐kynurenine limits A. phagocytophilum growth in tick cells. RNAi‐mediated knockdown of kynurenine aminotransferase expression results in increased ROS production and reduced A. phagocytophilum burden in tick cells. Collectively, these results suggest that l‐tryptophan pathway metabolites influence A. phagocytophilum survival by affecting build up of ROS levels in tick cells.

中文翻译：

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立克次体病原体使用节肢动物色氨酸途径代谢物来逃避蜱细胞中的活性氧。

病原体感染后诱导的活性氧 (ROS) 在宿主防御中起着重要作用。立克次体病原体无形体吞噬细胞，主要由美国肩胛硬蜱传播，已经进化出许多策略来逃避 ROS 并在哺乳动物细胞中存活。然而，关于 ROS在蜱中A. phagocytophilum感染中的作用知之甚少。我们的结果表明A. phagocytophilum和 hemin 诱导蜱细胞中l-色氨酸途径的激活。黄嘌呤酸 (XA) 是一种色氨酸代谢物，通过抑制色氨酸双加氧酶 (TDO) 活性来支持蜱细胞中嗜噬细胞杆菌的生长，从而导致l-犬尿氨酸水平随后影响 ROS 的积累。然而，血红素通过诱导 TDO 活性导致l-犬尿氨酸水平增加和 ROS 产生来支持A. phagocytophilum在蜱细胞中的生长。我们的数据显示 XA 和犬尿氨酸 (KA) 螯合血红素。此外，用 3-羟基l-犬尿氨酸处理蜱细胞会限制A. phagocytophilum在蜱细胞中的生长。RNAi 介导的犬尿氨酸氨基转移酶表达的敲低导致蜱细胞中ROS 产生增加并减少A. phagocytophilum负担。总的来说，这些结果表明l-色氨酸途径代谢物影响A. phagocytophilum 通过影响蜱细胞中 ROS 水平的积累来提高存活率。