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<p>Chronic liver fluke infections represent a major global health burden, driving liver fibrosis and elevating cancer risk, yet the immunological mechanisms linking persistent infection to tissue damage remain poorly defined. Using <i>Clonorchis sinensis</i>, a carcinogenic liver fluke infecting millions worldwide, as a representative model, we map immune responses during chronic infection in mice. We show that intrahepatic CD8⁺ tissue-resident memory T cells (T<sub>RM</sub>) progressively accumulate and drive pathology by producing chemokines that promote immune recruitment and fibroblast activation. Depletion of CD8⁺ T cells during defined disease phases markedly alleviates liver inflammation and fibrosis, demonstrating their causal role. Strikingly, C-C motif chemokine ligand 4, predominantly secreted by CD8⁺ T<sub>RM</sub> cells, correlates with fibrosis severity in both experimental models and patient cohorts, establishing it as a circulating biomarker for noninvasive disease monitoring. These findings define a pathogenic CD8⁺ T<sub>RM</sub>–chemokine axis underlying helminth-induced liver injury and highlight T<sub>RM</sub>-derived chemokines as biomarkers and therapeutic targets for fibrosis across chronic parasitic infections.</p>

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A pathogenic CD8⁺ TRM–chemokine axis orchestrates liver fibrosis and provides circulating biomarkers during chronic Clonorchis sinensis infection

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月31日

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  • Xinyue Du,
  • Jiashun Li,
  • Xin Wang,
  • Wenyu Wu,
  • Tingjun Zhu,
  • Huibo Yan,
  • Chenyun Wu,
  • Yuanyuan Li,
  • Yuwei Gao,
  • Haibo Yi,
  • Kokouvi Kassegne,
  • Xiangwei Li,
  • Xiaoyin Niu,
  • Helena Helmby,
  • Samuel C. Wassmer,
  • Youqiong Ye,
  • Banchob Sripa,
  • Guangjie Chen,
  • Menbao Qian,
  • Zhaojun Wang

摘要

Chronic liver fluke infections represent a major global health burden, driving liver fibrosis and elevating cancer risk, yet the immunological mechanisms linking persistent infection to tissue damage remain poorly defined. Using Clonorchis sinensis, a carcinogenic liver fluke infecting millions worldwide, as a representative model, we map immune responses during chronic infection in mice. We show that intrahepatic CD8⁺ tissue-resident memory T cells (TRM) progressively accumulate and drive pathology by producing chemokines that promote immune recruitment and fibroblast activation. Depletion of CD8⁺ T cells during defined disease phases markedly alleviates liver inflammation and fibrosis, demonstrating their causal role. Strikingly, C-C motif chemokine ligand 4, predominantly secreted by CD8⁺ TRM cells, correlates with fibrosis severity in both experimental models and patient cohorts, establishing it as a circulating biomarker for noninvasive disease monitoring. These findings define a pathogenic CD8⁺ TRM–chemokine axis underlying helminth-induced liver injury and highlight TRM-derived chemokines as biomarkers and therapeutic targets for fibrosis across chronic parasitic infections.