The large intestine harbors microorganisms playing unique roles in host physiology. The beneficial or detrimental outcome of host-microbiome coexistence depends largely on the balance between regulators and responder intestinal CD4⁺ T cells. We found that ulcerative colitis-like changes in the large intestine after infection with the protist Blastocystis ST7 in a mouse model are associated with reduction of anti-inflammatory Treg cells and simultaneous expansion of pro-inflammatory Th17 responders. These alterations in CD4⁺ T cells depended on the tryptophan metabolite indole-3-acetaldehyde (I3AA) produced by this single-cell eukaryote. I3AA reduced the Treg subset in vivo and iTreg development in vitro by modifying their sensing of TGFβ, concomitantly affecting recognition of self-flora antigens by conventional CD4⁺ T cells. Parasite-derived I3AA also induces over-exuberant TCR signaling, manifested by increased CD69 expression and downregulation of co-inhibitor PD-1. We have thus identified a new mechanism dictating CD4⁺ fate decisions. The findings thus shine a new light on the ability of the protist microbiome and tryptophan metabolites, derived from them or other sources, to modulate the adaptive immune compartment, particularly in the context of gut inflammatory disorders.

中文翻译：

---

由肠道微生物组真核生物产生的色氨酸代谢物诱导促炎性 T 细胞

大肠中蕴藏着在宿主生理学中发挥独特作用的微生物。宿主-微生物组共存的有益或有害结果在很大程度上取决于调节剂和应答者肠道 CD4 ⁺ T 细胞之间的平衡。我们发现，在小鼠模型中感染原生生物芽囊菌ST7后，大肠发生类似溃疡性结肠炎的变化，与抗炎性 Treg 细胞的减少和促炎性 Th17 反应细胞的同时扩张有关。CD4 ⁺ T 细胞中的这些改变取决于这种单细胞真核生物产生的色氨酸代谢物吲哚-3-乙醛 (I3AA)。I3AA 通过改变 TGFβ 的感应来减少体内Treg 亚群和体外 iTreg 的发育，同时影响传统 CD4 ⁺ T 细胞对自身菌群抗原的识别。寄生虫源性 I3AA 还会诱导过度活跃的 TCR 信号传导，表现为 CD69 表达增加和共抑制剂 PD-1 下调。因此，我们确定了一种决定 CD4 ⁺命运的新机制。因此，这些发现为原生微生物组和源自它们或其他来源的色氨酸代谢物调节适应性免疫区室的能力提供了新的线索，特别是在肠道炎症性疾病的背景下。