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<p>Rupture of hydatid cysts caused by <i>Echinococcus granulosus</i> represents a critical clinical emergency in patients with echinococcosis. It frequently triggers severe allergic reactions including anaphylactic shock, which is often accompanied by acute lung injury and prolonged recovery. Although the early inflammatory phase of this response has been extensively characterized, the immune mechanisms that sustain lung injury during the post-shock recovery phase, particularly those involving CD8 + T cells, remain poorly understood. A murine model of anaphylactic shock was established by sensitizing mice to E. granulosus cystic fluid. Key immune-related pathways were identified using an integrated bioinformatics approach that included GeneCards screening, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction. Lung injury was assessed using a TUNEL assay. Immune cell subsets in the lung tissue, especially CD8 + T cells, were quantified and molecular changes were evaluated using western blotting and quantitative real-time PCR (qRT-PCR). Bioinformatics analysis revealed significant enrichment of genes associated with CD8 + T cell activity and allergic inflammation within the TGF-β-PI3K/AKT signaling pathway. In vivo, anaphylactic shock markedly increased macrophage infiltration in lung tissue while concurrently reducing PD-L1-mediated inhibitory signaling toward CD8 + T cells. Consequently, substantial accumulation of CD8 + T cells, elevated granzyme B expression, severe disruption of alveolar architecture, and increased cellular apoptosis were observed. Pharmacological modulation of the TGF-β pathway significantly altered cytokine production by CD8 + T cells, regulated downstream PI3K/AKT activation and inflammatory cytokine expression (e.g., IL-1β and TNF-α), and correspondingly ameliorated or exacerbated lung injury. Notably, CD8 + T cell-driven activation of the TGF-β-PI3K/AKT axis persisted during the recovery phase (48–72&#xa0;h) following an acute anaphylactic episode. Our findings demonstrate that sustained activation of the TGF-β-PI3K/AKT-CD8<sup>+</sup> T cell axis is a pivotal mechanism contributing to CD8 + T cell-mediated immunopathology and lung injury following E. granulosus-induced anaphylactic shock. This pathway not only operates during the acute phase but also critically influences pulmonary repair during recovery. Therefore, targeting the TGF-β-PI3K/AKT-CD8<sup>+</sup> T cell axis during the post-shock recovery window may offer a promising therapeutic strategy to accelerate pulmonary rehabilitation and mitigate long-term complications.</p>

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Impact of CD8+ T cells on lung injury prognosis via the TGF-β-PI3K/AKT axis in Echinococcus granulosus cyst fluid-induced anaphylaxis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Chunsheng Wang,
  • Guligeiya Parehati,
  • Chenxi Zhou,
  • Jianrong Ye

摘要

Rupture of hydatid cysts caused by Echinococcus granulosus represents a critical clinical emergency in patients with echinococcosis. It frequently triggers severe allergic reactions including anaphylactic shock, which is often accompanied by acute lung injury and prolonged recovery. Although the early inflammatory phase of this response has been extensively characterized, the immune mechanisms that sustain lung injury during the post-shock recovery phase, particularly those involving CD8 + T cells, remain poorly understood. A murine model of anaphylactic shock was established by sensitizing mice to E. granulosus cystic fluid. Key immune-related pathways were identified using an integrated bioinformatics approach that included GeneCards screening, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction. Lung injury was assessed using a TUNEL assay. Immune cell subsets in the lung tissue, especially CD8 + T cells, were quantified and molecular changes were evaluated using western blotting and quantitative real-time PCR (qRT-PCR). Bioinformatics analysis revealed significant enrichment of genes associated with CD8 + T cell activity and allergic inflammation within the TGF-β-PI3K/AKT signaling pathway. In vivo, anaphylactic shock markedly increased macrophage infiltration in lung tissue while concurrently reducing PD-L1-mediated inhibitory signaling toward CD8 + T cells. Consequently, substantial accumulation of CD8 + T cells, elevated granzyme B expression, severe disruption of alveolar architecture, and increased cellular apoptosis were observed. Pharmacological modulation of the TGF-β pathway significantly altered cytokine production by CD8 + T cells, regulated downstream PI3K/AKT activation and inflammatory cytokine expression (e.g., IL-1β and TNF-α), and correspondingly ameliorated or exacerbated lung injury. Notably, CD8 + T cell-driven activation of the TGF-β-PI3K/AKT axis persisted during the recovery phase (48–72 h) following an acute anaphylactic episode. Our findings demonstrate that sustained activation of the TGF-β-PI3K/AKT-CD8+ T cell axis is a pivotal mechanism contributing to CD8 + T cell-mediated immunopathology and lung injury following E. granulosus-induced anaphylactic shock. This pathway not only operates during the acute phase but also critically influences pulmonary repair during recovery. Therefore, targeting the TGF-β-PI3K/AKT-CD8+ T cell axis during the post-shock recovery window may offer a promising therapeutic strategy to accelerate pulmonary rehabilitation and mitigate long-term complications.