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Background <p>The kynurenine pathway (KP), central to tryptophan metabolism, regulates neuroimmune interactions in vertebrates through the dual actions of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). However, crustaceans lack IDO and rely solely on TDO, yet the tissue-specific roles of TDO in this lineage remain unknown. Using&#xa0;<i>Litopenaeus vannamei</i>, a key aquaculture species, we investigated how TDO-mediated KP adapts to functional constraints in neural and respiratory tissues.</p> Results <p>Genomic analyses confirmed the absence of&#xa0;<i>IDO</i>&#xa0;in crustaceans, while&#xa0;<i>LvTDO</i>&#xa0;retained catalytic domains homologous to vertebrates but acquired lineage-specific structural features. Tissue-specific profiling revealed dominant&#xa0;<i>LvTDO</i>&#xa0;expression in brain and gill. RNAi knockdown triggered distinct responses: the brain upregulated oxidative phosphorylation and cytoskeletal pathways but suppressed neural signaling, whereas the gill activated apoptosis and immune pathways while downregulating glycolysis. KEGG analysis further highlighted hypoxia adaptation in gill (HIF-1 pathway) and stress signaling in brain (MAPK/Hippo).</p> Conclusions <p>Our findings suggest that&#xa0;<i>L. vannamei</i>&#xa0;may compensate for IDO absence via tissue-specific TDO regulation, with brain-gill axis specialization reflecting adaptive metabolic plasticity. While structural divergences in LvTDO hint at evolutionary innovations, functional equivalence to vertebrate IDO/TDO systems requires further validation. This study highlights the evolutionary flexibility of KP in invertebrates, though metabolite dynamics and long-term physiological impacts remain to be explored.</p>

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TDO-mediated tissue-specific regulation of kynurenine pathway in the brain and gill of Litopenaeus vannamei

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月26日

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  • Guiling Tan,
  • Hao Yang,
  • Jingxuan Liang,
  • Jiayue Yin,
  • Xin Zhang,
  • Yuying Sun

摘要

Background

The kynurenine pathway (KP), central to tryptophan metabolism, regulates neuroimmune interactions in vertebrates through the dual actions of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). However, crustaceans lack IDO and rely solely on TDO, yet the tissue-specific roles of TDO in this lineage remain unknown. Using Litopenaeus vannamei, a key aquaculture species, we investigated how TDO-mediated KP adapts to functional constraints in neural and respiratory tissues.

Results

Genomic analyses confirmed the absence of IDO in crustaceans, while LvTDO retained catalytic domains homologous to vertebrates but acquired lineage-specific structural features. Tissue-specific profiling revealed dominant LvTDO expression in brain and gill. RNAi knockdown triggered distinct responses: the brain upregulated oxidative phosphorylation and cytoskeletal pathways but suppressed neural signaling, whereas the gill activated apoptosis and immune pathways while downregulating glycolysis. KEGG analysis further highlighted hypoxia adaptation in gill (HIF-1 pathway) and stress signaling in brain (MAPK/Hippo).

Conclusions

Our findings suggest that L. vannamei may compensate for IDO absence via tissue-specific TDO regulation, with brain-gill axis specialization reflecting adaptive metabolic plasticity. While structural divergences in LvTDO hint at evolutionary innovations, functional equivalence to vertebrate IDO/TDO systems requires further validation. This study highlights the evolutionary flexibility of KP in invertebrates, though metabolite dynamics and long-term physiological impacts remain to be explored.