The local immune mechanisms responsible for either self-healing or sustained chronic infection are not clear, in the development of E. multilocularis larvae. Here, we developed a suitable experimental model that mimics naturally infected livers, according to the parasite load. We demonstrated that local cellular immunity and fibrogenesis are actually protective and fully able to limit metacestode growth in the liver of low or medium dose-infected mice (LDG or MDG), or even to clear it, while impairment of cellular immunity is followed by a more rapid and severe course of the disease in high dose-infected mice (HDG). And recruitment and/ or proliferation of memory T cells (including CD4 Tem, CD8 Tcm and CD8 Tem) and imbalance of T1/T2/T17/Treg-type T cells in liver were not only associated with clearance of the parasite infection in LDG, but also with increased hepatic injury in HDG; in particular the dual role of CD8 T cells depending on the parasite load and the various stages of metacestode growth. Besides, we first demonstrate the association between LAG3- or 2B4-expressing T cells exhaustion and HD inocula in late stages. Our quantitative experimental model appears fully appropriate to study immunomodulation as a therapeutic strategy for patients with Alveolar Echinococcosis.
Background and Aims
The cestode Echinococcus multilocularis infection, a serious health problem worldwide, causes alveolar echinococcosis (AE), a tumor‐like disease predominantly located in the liver and able to spread to any organs. Until now, there have been few studies that explore how T‐cell exhaustion contributes to the parasite’s escape from immune attack and how it might be reversed.
Approach and Results
In this study, we found that liver T‐cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT) expression was significantly enhanced and positively correlated with lesion activity in AE patients. High TIGIT expression in both liver‐infiltrating and blood T cells was associated with their functional exhaustion, and its ligand CD155 was highly expressed by hepatocytes surrounding the infiltrating lymphocytes. In co‐culture experiments using human blood T cells and hepatic cell line HL‐7702, CD155 induced functional impairment of TIGIT+ T cells, and in vitro blockade with TIGIT antibody restored the function of AE patients’ T cells. Similar TIGIT‐related functional exhaustion of hepatic T cells and an abundant CD155 expression on hepatocytes were observed in E. multilocularis–infected mice. Importantly, in vivo blocking TIGIT prevented T‐cell exhaustion and inhibited disease progression in E. multilocularis–infected mice. Mechanistically, CD4+ T cells were totally and CD8+ T cells partially required for anti‐TIGIT–induced regression of parasite growth in mice.
Conclusions
This study demonstrates that E. multilocularis can induce T‐cell exhaustion through inhibitory receptor TIGIT, and that blocking this checkpoint may reverse the functional impairment of T cells and represent a possible approach to immunotherapy against AE.
AIM:To evaluate the reliability and accuracy of threedimensional (3D) reconstruction for liver resection in patients with hepatic alveolar echinococcosis (HAE).
METHODS:One-hundred and six consecutive patients with HAE underwent hepatectomy at our hospital between May 2011 and January 2015. Fifty-nine patients underwent preoperative 3D reconstruction and "virtual" 3D liver resection before surgery (Group A). Another 47 patients used conventional imaging methods for preoperative assessment (Group B). Outcomes of hepatectomy were compared between the two groups.
RESULTS:There was no significant difference in preoperative data between the two groups. groups had good correlation with actual graft weight (Group A: r = 0.978; Group B: r = 0.960). There was a significant higher serum level of albumin in Group A (26.3 ± 5.9 vs 22.6 ± 4.3 g/L, P < 0.05). Other postoperative laboratory parameters (serum levels of aminotransferase and bilirubin; prothrombin time) and duration of postoperative hospital stay were similar. Sixteen complications occurred in Group A and 19 in Group B. All patients were followed for 3-46 (mean, 17.3) mo. There was no recurrence of lesions in Group A, but two recurrences in Group B. There were three deaths: two from cerebrovascular accident, and one from car accident.
CONCLUSION:3D reconstruction provides comprehensive and precise anatomical information for the liver. It also improves the chance of success and reduces the risk of hepatectomy in HAE. Core tip: With the rapid development of digital medicine, three-dimensional (3D) reconstruction software has become a new tool in surgery, and it is a quantitative imaging analysis system that provides real-time interactive tools for presurgical evaluation and planning. We compared the clinical results of hepatectomy for hepatic alveolar echinococcosis based on 3D software with traditional assessment. We found that liver resection based on 3D reconstruction was more effective in the diagnosis and treatment of HAE than techniques without 3D reconstruction. Such 3D reconstruction software for preoperative evaluation and surgical planning could increase the chance of success of surgery and reduce operative risk.
Cystic echinococcosis (CE) (hydatidosis, hydatid disease) is a zoonosis caused by the larval stage of Echinococcus granulosus, typically affecting the liver. Hepatic cystic echinococcosis (HCE) is often asymptomatic, and symptoms occur largely when complications develop. Up to one-third of HCE can be shown their complications such as rupture of the cyst, secondary infection, and anaphylactic reaction. Clinically, patients present with pain, obstructive jaundice, cholangitis, anaphylactic reaction, and shock. Early diagnosis and treatment of complications of CE must be very important, since mortality is high when obstruction of the biliary ducts occurs, leading to ascending cholangitis and septicemia, anaphylactic shock, or even life-threatening conditions.
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