Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host–pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxykynurenine (3-HK) protects from lethal bacterial infection. 3-HK, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages through a systemic mechanism that targets kainate-sensitive glutamate receptors. These findings reveal a new pathway by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with important implications for the coordination between the immune and nervous systems in pathological conditions.

细菌感染涉及病原体和宿主之间复杂的相互作用，其中感染的结果不仅仅取决于病原体的根除。为了识别通过改变宿主-病原体动态来促进宿主生存的小分子，我们使用斑马鱼胚胎进行了体内化学筛选，发现用 3-羟基犬尿氨酸 (3-HK) 治疗可以防止致命的细菌感染。 3-HK 是一种通过宿主色氨酸代谢产生的代谢物，没有直接的抗菌活性，但通过针对红藻氨酸敏感的谷氨酸受体的系统机制限制巨噬细胞中的细菌扩张，从而提高宿主的存活率。这些发现揭示了色氨酸代谢和红藻氨酸敏感性谷氨酸受体发挥作用并相互作用以调节免疫的新途径，对病理条件下免疫系统和神经系统之间的协调具有重要意义。