<i>Echinococcus multilocularis</i> vesicular fluid induces the expression of immune checkpoint proteins in vitro

Bellanger, Anne‐Pauline; Courquet, Sandra; Pallandre, Jean-René; Godet, Yann; Millon, Laurence

doi:10.1111/pim.12711

Cited by 12 publications

(10 citation statements)

References 19 publications

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“…( 28,29 ) Furthermore, Em ‐VF induces the expression of inhibitory receptors (including PD‐1, LAG‐3, and TIM‐3) on the surface of NK cells and inhibits NK cell activation and proliferation ex vivo . ( 12 ) Hence, these results suggest that Fgl2, IL‐27, or E. multilocularis –derived antigens might contribute to up‐regulated expression of TIGIT in NK cells during echinococcosis.…”

Section: Discussionmentioning

confidence: 78%

“…( 15 ) Available data have shown that E. multilocularis and its antigen inhibit the function of NK cells by up‐regulating the expression of inhibitory receptors, including NKG2A, PD‐1, and LAG‐3. ( 12 ) We found that NK cells from the blood and CLT of AE patients expressed a higher level of inhibitory receptor TIGIT, which was reported to inhibit the activation of NK cells in tumors or chronic infection. ( 18,23 ) Our study showed that TIGIT + NK cells in the peripheral blood or CLT of AE patients were functionally exhausted with lower expression of granzyme B, perforin, IFN‐γ, and TNF‐α.…”

Section: Discussionmentioning

confidence: 95%

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Involvement of TIGIT in Natural Killer Cell Exhaustion and Immune Escape in Patients and Mouse Model With Liver Echinococcus multilocularis Infection

Zhang

Wang

et al. 2021

Hepatology

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Background and Aims Alveolar echinococcosis (AE) is a lethal helminthic liver disease caused by persistent infection with Echinococcus multilocularis. Although more attention has been paid to the immunotolerance of T cells caused by E. multilocularis infection, the role of natural killer (NK) cell, a critical player in liver immunity, is seldom studied. Approach and Results Here, we observed that NK cells from the blood and closed liver tissue (CLT) of AE patients expressed a higher level of inhibitory receptor TIGIT and were functionally exhausted with a lower expression of granzyme B, perforin, interferon‐gamma (IFN‐γ), and TNF‐α. Addition of anti‐TIGIT (T‐cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain) monoclonal antibody into AE patients’ peripheral blood mononuclear cell culture significantly enhanced the synthesis of IFN‐γ and TNF‐α by NK cells, indicating the reversion of exhausted NK cells by TIGIT blockade. In the mouse model of E. multilocularis infection, liver and splenic TIGIT+ NK cells progressively increased dependent of infection dosage and timing and were less activated and less degranulated with lower cytokine secretion. Furthermore, TIGIT deficiency or blockade in vivo inhibited liver metacestode growth, reduced liver injury, and increased the level of IFN‐γ produced by liver NK cells. Interestingly, NK cells from mice with persistent chronic infection expressed a higher level of TIGIT compared to self‐healing mice. To look further into the mechanisms, more regulatory CD56bright and murine CD49a+ NK cells with higher TIGIT expression existed in livers of AE patients and mice infected with E. multilocularis, respectively. They coexpressed higher surface programmed death ligand 1 and secreted more IL‐10, two strong inducers to mediate the functional exhaustion of NK cells. Conclusions Our results indicate that inhibitory receptor TIGIT is involved in NK cell exhaustion and immune escape from E. multilocularis infection.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 95%

Involvement of TIGIT in Natural Killer Cell Exhaustion and Immune Escape in Patients and Mouse Model With Liver Echinococcus multilocularis Infection

Zhang

Wang

et al. 2021

Hepatology

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“…Other supporting research was found to be in agreement with the above inference. Confirmation of this hypothesis was brought about by a control in the infection utilising immunotherapy which acted on PD-L1 pathway blockage [72,73].…”

Section: Immune Checkpoint Inhibitormentioning

confidence: 92%

Perspective Chapter: Prospects for Pharmacological Therapy of Hepatic Alveolar Echinococcosis

Mohan¹,

Gupta²,

Lal³

2023

Infectious Diseases

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Often misdiagnosed as liver cancer at first, the Alveolar hydatid disease or hepatic alveolar echinococcosis is an uncommon but potentially harmful variant of the disease also synonymously known as Echinococcus multilocularis (E. Multilocularis). The major area being drastically affected is the liver, from where its later advances into the lung and brain, typically fatal if left untreated. Even if surgery is still the recommended course of treatment for the condition, drug therapy cannot be thwarted off and remains essential and vital for individuals with disease extremity. This chapter therefore aims to present a framework through which FDA-approved drugs and nano drug delivery technologies collaborate to manage progressive hepatic alveolar echinococcosis.

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“…Last, there are many diseases in which immune checkpoints seem to be highly important, e.g., parasitic infections such as helminthiasis, toxoplasmosis, and malaria ( 8 , 148 , 149 ), yet further research is necessary to develop effective therapeutic approaches.…”

Section: Concluding Remarks and New Directionsmentioning

confidence: 99%

The Role of Immune Checkpoint Molecules on Macrophages in Cancer, Infection, and Autoimmune Pathologies

et al. 2022

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Immune checkpoint inhibitors have revolutionized immunotherapy against various cancers over the last decade. The use of checkpoint inhibitors results in remarkable re-activation of patients’ immune system, but is also associated with significant adverse events. In this review, we emphasize the importance of cell-type specificity in the context of immune checkpoint-based interventions and particularly focus on the relevance of macrophages. Immune checkpoint blockade alters the dynamic macrophage phenotypes and thereby substantially manipulates therapeutical outcome. Considering the macrophage-specific immune checkpoint biology, it seems feasible to ameliorate the situation of patients with severe side effects and even increase the probability of survival for non-responders to checkpoint inhibition. Apart from malignancies, investigating immune checkpoint molecules on macrophages has stimulated their fundamental characterization and use in other diseases as well, such as acute and chronic infections and autoimmune pathologies. Although the macrophage-specific effect of checkpoint molecules has been less studied so far, the current literature shows that a macrophage-centered blockade of immune checkpoints as well as a stimulation of their expression represents promising therapeutic avenues. Ultimately, the therapeutic potential of a macrophage-focused checkpoint therapy might be maximized by diagnostically assessing individual checkpoint expression levels on macrophages, thereby personalizing an effective treatment approach for each patient having cancer, infection, or autoimmune diseases.

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Echinococcus multilocularis vesicular fluid induces the expression of immune checkpoint proteins in vitro

Cited by 12 publications

References 19 publications

Involvement of TIGIT in Natural Killer Cell Exhaustion and Immune Escape in Patients and Mouse Model With Liver Echinococcus multilocularis Infection

Involvement of TIGIT in Natural Killer Cell Exhaustion and Immune Escape in Patients and Mouse Model With Liver Echinococcus multilocularis Infection

Perspective Chapter: Prospects for Pharmacological Therapy of Hepatic Alveolar Echinococcosis

The Role of Immune Checkpoint Molecules on Macrophages in Cancer, Infection, and Autoimmune Pathologies

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