Centre for Animal Health Innovation, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.
School of Life Sciences, University of Technology, Sydney, New South Wales, Australia.
Infect Immun. 2018 Mar 22;86(4). doi: 10.1128/IAI.00714-17. Print 2018 Apr.
is an important intracellular bacterium that causes a range of diseases in animals, including a native Australian marsupial, the koala. In humans and animals, a gamma interferon (IFN-γ)-mediated immune response is important for the control of intracellular bacteria. The present study tested the hypotheses that can escape IFN-γ-mediated depletion of host cell tryptophan pools. In doing so, we demonstrated that, unlike , is completely resistant to IFN-γ in human epithelial cells. While the growth of was inhibited in tryptophan-deficient medium, it could be restored by the addition of kynurenine, anthranilic acid, and indole, metabolites that could be exploited by the gene products of the tryptophan biosynthesis operon. We also found that expression of genes was detectable only when was grown in tryptophan-free medium, with gene repression occurring in response to the addition of kynurenine, anthranilic acid, and indole. When grown in bovine kidney epithelial cells, bovine IFN-γ also failed to restrict the growth of , while was inhibited, suggesting that could use the same mechanisms to evade the immune response in its natural host. Highlighting the different mechanisms triggered by IFN-γ, however, both species failed to grow in murine McCoy cells treated with murine IFN-γ. This work confirms previous hypotheses about the potential survival of after IFN-γ-mediated host cell tryptophan depletion and raises questions about the immune pathways used by the natural hosts of to control the widespread pathogen.
是一种重要的细胞内细菌,可导致包括澳大利亚本土有袋动物树袋熊在内的多种动物患病。在人类和动物中,γ干扰素(IFN-γ)介导的免疫反应对于控制细胞内细菌至关重要。本研究检验了以下假设:可以逃避 IFN-γ 介导的宿主细胞色氨酸池耗竭。通过这样做,我们证明了与 不同, 完全抵抗人类上皮细胞中的 IFN-γ。虽然在色氨酸缺乏的培养基中 的生长受到抑制,但通过添加犬尿氨酸、邻氨基苯甲酸和吲哚可以恢复生长,这些代谢物可以被 的色氨酸生物合成操纵子的基因产物利用。我们还发现,只有在无色氨酸培养基中生长时,才可以检测到 的基因表达,而当添加犬尿氨酸、邻氨基苯甲酸和吲哚时,基因表达受到抑制。当在牛肾上皮细胞中生长时,牛 IFN-γ 也不能限制 的生长,而 受到抑制,这表明 可以利用相同的机制逃避其天然宿主的免疫反应。然而,当生长在经鼠 IFN-γ 处理的鼠 McCoy 细胞中时,两种物种都无法生长,这突出了 IFN-γ 触发的不同机制。这项工作证实了先前关于 在 IFN-γ 介导的宿主细胞色氨酸耗竭后可能存活的假设,并提出了关于 天然宿主用来控制广泛存在的病原体的免疫途径的问题。