Natural killer cell dysfunction in hepatic alveolar echinococcosis: an under-recognized cytotoxic node in parasite immune escape
4 affiliations
- 1Qinghai University
- 2Qinghai University Affiliated Hospital
- 3Qinghai Institute for Endemic Disease Prevention and Control
- 4Department of Hepatobiliary and Pancreatic Surgery, Qinghai University Affiliated Hospital
Abstract
Alveolar echinococcosis (AE), caused by the larval stage of Echinococcus multilocularis , is a chronic and infiltrative hepatic helminth infection characterized by tumor-like growth, progressive tissue destruction and long-term host-parasite coexistence. Parasite persistence in the liver is sustained not only by local invasion but also by a progressively remodeled immune microenvironment. Most immunological studies of AE have focused on macrophages, neutrophils, regulatory T cells, dendritic cells, T-cell exhaustion and fibrosis. By contrast, natural killer (NK) cells have remained a relatively under-integrated component of AE immunology, despite the liver being enriched in NK and innate lymphoid populations. Accumulating evidence indicates that NK activity is reduced in AE patients, that E. multilocularis vesicular fluid can suppress NK-cell activation and proliferation, and that inhibitory receptors including NKG2A and TIGIT are associated with impaired NK-derived IFN-γ, TNF-α, granzyme B and perforin responses in patients and experimental models. Recent work on checkpoint signaling, suppressive immune niches and fibrotic spatial organization further suggests that NK-cell dysfunction should not be interpreted as an isolated NK-intrinsic event. Instead, it may represent an under-recognized cytotoxic node within a parasite-induced hepatic immune escape network shaped by parasite-derived products, myeloid remodeling, Treg/DC crosstalk, inhibitory receptor-ligand interactions and fibrotic immune segregation. In this review, we synthesize the evidence for NK-cell dysfunction in AE, compare the strength of support for NKG2A, TIGIT, inhibitory KIRs and TIM-3/LAG-3-related pathways, and propose an NK-oriented framework for integrating cytotoxic immune dysfunction with parasite persistence and fibrosis-associated lesion remodeling. We also highlight unresolved questions regarding direct versus indirect antiparasitic NK functions, liver-resident NK cells, NK-ILC1-NKT boundaries, receptor-ligand sources and checkpoint-targeted immunomodulation in AE.
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BibTeX
@article{wang2026natural,
title = {{Natural killer cell dysfunction in hepatic alveolar echinococcosis: an under-recognized cytotoxic node in parasite immune escape}},
author = {Shilong Wang and Kerong Lu and Chao Jiang and Yongqiang Zou and Dalin Shi and Mingquan Pang and Cipeng Fan and Zhixin Wang and Manjun Deng and Chengwei Tie and Haining Fan},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1976611},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976611/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Natural killer cell dysfunction in hepatic alveolar echinococcosis: an under-recognized cytotoxic node in parasite immune escape
AU - Shilong Wang
AU - Kerong Lu
AU - Chao Jiang
AU - Yongqiang Zou
AU - Dalin Shi
AU - Mingquan Pang
AU - Cipeng Fan
AU - Zhixin Wang
AU - Manjun Deng
AU - Chengwei Tie
AU - Haining Fan
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1976611
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976611/full
AB - Alveolar echinococcosis (AE), caused by the larval stage of Echinococcus multilocularis , is a chronic and infiltrative hepatic helminth infection characterized by tumor-like growth, progressive tissue destruction and long-term host-parasite coexistence. Parasite persistence in the liver is sustained not only by local invasion but also by a progressively remodeled immune microenvironment. Most immunological studies of AE have focused on macrophages, neutrophils, regulatory T cells, dendritic cells, T-cell exhaustion and fibrosis. By contrast, natural killer (NK) cells have remained a relatively under-integrated component of AE immunology, despite the liver being enriched in NK and innate lymphoid populations. Accumulating evidence indicates that NK activity is reduced in AE patients, that E. multilocularis vesicular fluid can suppress NK-cell activation and proliferation, and that inhibitory receptors including NKG2A and TIGIT are associated with impaired NK-derived IFN-γ, TNF-α, granzyme B and perforin responses in patients and experimental models. Recent work on checkpoint signaling, suppressive immune niches and fibrotic spatial organization further suggests that NK-cell dysfunction should not be interpreted as an isolated NK-intrinsic event. Instead, it may represent an under-recognized cytotoxic node within a parasite-induced hepatic immune escape network shaped by parasite-derived products, myeloid remodeling, Treg/DC crosstalk, inhibitory receptor-ligand interactions and fibrotic immune segregation. In this review, we synthesize the evidence for NK-cell dysfunction in AE, compare the strength of support for NKG2A, TIGIT, inhibitory KIRs and TIM-3/LAG-3-related pathways, and propose an NK-oriented framework for integrating cytotoxic immune dysfunction with parasite persistence and fibrosis-associated lesion remodeling. We also highlight unresolved questions regarding direct versus indirect antiparasitic NK functions, liver-resident NK cells, NK-ILC1-NKT boundaries, receptor-ligand sources and checkpoint-targeted immunomodulation in AE.
SN - 1664-3224
ER -