Immunology of Alveolar and Cystic Echinococcosis (AE and CE)

Gottstein, Bruno; Soboslay, Peter T.; Ortona, Elena; Wang, Junhua; Siracusano, Alessandra; Vuitton, Dominique A.

doi:10.1016/bs.apar.2016.09.005

Cited by 106 publications

(96 citation statements)

References 192 publications

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“…TIGIT + Treg cells appear uniquely capable of suppressing T h 1‐type responses, as opposed to T h 2 responses . T‐cell exhaustion actually plays a role in E. multilocularis metacestode growth in addition to the well‐described immune tolerance mediated by Treg cells and regulatory cytokines in intermediate hosts with chronic infection . Although the precise mechanisms remain to be elucidated by further experiments, our findings showed that the treatment with anti‐TIGIT mAb reduced the liver metacestode load, together with a significantly increased T h 1‐type T‐cell response in liver and spleen, including elevated IL‐2, IFN‐γ, and TNF‐α production.…”

Section: Discussionmentioning

confidence: 68%

“…AE is a tumor‐like disease predominantly located in the liver and able to spread to any organ through local invasion and metastases . E. multilocularis is a successful parasite through its ability to shape an “immunosuppressive” microenvironment, leading to a kind of balance between pro‐ and anti‐inflammatory responses to maintain immune homoeostasis during persistent infection . However, different from intracellular bacteria and parasites that mostly live inside macrophages and have been extensively studied for the immunological mechanisms that govern their persistence/clearance, E. multilocularis, an extracellular pathogen, has received less attention, and studies on parasite‐host interactions are limited by the absence of specific infected target cells …”

mentioning

confidence: 99%

“…Many studies have shown that cellular immunity affects the development of AE lesions, and that AE is more severe, with a faster course, when there is some degree of impairment of the functional activity of T cells . Persistence of E. multilocularis is associated with a chronic granulomatous inflammation, leading to the disruption of the normal function of T cells, which is nowadays referred to as “functional exhaustion.” Recent reports have also shown that E. multilocularis infection is associated with the expression of “checkpoint” receptors that are known to limit the activity of parasite‐specific lymphocytes.…”

mentioning

confidence: 99%

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Immune Exhaustion of T Cells in Alveolar Echinococcosis Patients and Its Reversal by Blocking Checkpoint Receptor TIGIT in a Murine Model

Zhang

Lin

et al. 2020

Hepatology

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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.

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Section: Discussionmentioning

confidence: 68%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Immune Exhaustion of T Cells in Alveolar Echinococcosis Patients and Its Reversal by Blocking Checkpoint Receptor TIGIT in a Murine Model

Zhang

Lin

et al. 2020

Hepatology

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“…34 "Regressive cysts" in pigs, cattle, sheep and humans (cases) 74,80,81,99 "Late" "complicated" infections in paca 86 Human infections (in part of the lesion at least). 34,[93][94][95]156 Infections in gorillas 96…”

Section: Natural Infections In Pigs 98mentioning

confidence: 99%

Granulomatous responses in larval taeniid infections

Díaz

Sagasti

Casaravilla

2018

Parasite Immunology

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Granulomas are responses to persistent nonliving bodies or pathogens, centrally featuring specialized macrophage forms called epithelioid and multinucleated giant cells. The larval stages of the cestode parasites of the Taeniidae family (Taenia, Echinococcus) develop for years in fixed tissue sites in mammals. In consequence, they are targets of granulomatous responses. The information on tissue responses to larval taeniids is fragmented among host and parasite species and scattered over many decades. We attempt to draw an integrated picture of these responses in solid tissues. The intensity of inflammation around live parasites spans a spectrum from minimal to high, parasite vitality correlating with low inflammation. The low end of the inflammatory spectrum features collagen capsules proximal to the parasites and moderate distal infiltration. The middle of the spectrum is dominated by classical granulomatous responses, whereas the high end features massive eosinophil invasions. Across the range of parasite species, much observational evidence suggests that eosinophils are highly effective at killing larval taeniids in solid tissues, before and during chronic granulomatous responses. The evidence available also suggests that these parasites are adapted to inhibit host granulomatous responses, in part through the exacerbation of host regulatory mechanisms including regulatory T cells and TGF-β.

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“…The molecular mechanisms underlying its development and pathogenesis are still unclear [1][2][3], although it has been reported that this parasite can successfully escape host immune responses, and a number of immunoregulatory mechanisms related to macrophages and dendritic cells as well as regulatory T cells are potentially involved [2]. In our previous studies, we found that hydatid cysts of E. granulosus could promote the formation of tubes from human umbilical vein endothelial cells (HUVECs) in vitro [4], and that myeloid-derived suppressor cells (MDSCs) were significantly enriched in the spleen and peripheral blood of Balb/c mice infected with E. granulosus and played an immunosuppressive role [5].…”

Section: Introductionmentioning

confidence: 99%

Pro-Angiogenic Activity of Monocytic-Type Myeloid-Derived Suppressor Cells from Balb/C Mice Infected with Echinococcus Granulosus and the Regulatory Role of miRNAs

Yin¹,

Liu²,

Yu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study aims to predict the pro-angiogenic functions of monocytic-type myeloid-derived suppressor cells (M-MDSCs) derived from mice infected with Echinococcus granulosus. Methods: M-MDSCs were collected from Balb/c mice infected with E. granulosus and normal mice (control) and cultured in vitro. Human umbilical vein endothelial cells (HUVECs) were stimulated with the cell supernatant, and angiogenesis was investigated and analysed by the Angiogenesis module of the software NIH Image J. RNA was extracted from fresh isolated M-MDSCs and analysed with miRNA microarray; differentially expressed miRNAs and their potential functions were analysed through several bioinformatics tools. Finally, quantitative PCR was used to confirm the results of microarray analysis. Results: M-MDSCs from mice infected with E. granulosus could promote the formation of tubes from HUVECs in vitro. Moreover, vascular endothelial growth factor (VEGF) showed significantly high expression, whereas soluble fms-like tyrosine kinase-1 (sFlt-1) showed low expression at the transcriptional level in M-MDSCs from mice infected with E. granulosus. Microarray analysis of miRNAs showed that 28 miRNAs were differentially expressed in M-MDSCs from the two experimental mice groups, and 272 target genes were predicted using the microRNA databases TargetScan, PITA and microRNAorg. These target genes were mainly involved in the biological processes of intracellular protein transport, protein targeting to the lysosome and protein transport, and mainly located in the cytoplasm, neuronal cell body and membrane. Moreover, they were mainly involved in the molecular functions of protein binding, metal ion binding and SH3 domain binding. Further, the differentially expressed miRNAs were mainly enriched in the endocytosis, Wnt and axon guidance pathways, as well as the MAPK, focal adhesion, PI3K-Akt, cAMP, mTOR and TGF-β signalling pathways, which are linked to immunoregulation and angiogenesis based on the results of bioinformatics analysis with DIANA-miRPath 3.0. In addition, the expression of eight miRNAs was randomly verified by quantitative PCR independently in three mice infected with E. granulosus and three normal mice. Conclusion: M-MDSCs have a potential angiogenic role during E. granulosus infection, and miRNAs may play a role in the immune response and angiogenesis functions of M-MDSCs through regulation of the identified signalling pathways.

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Immunology of Alveolar and Cystic Echinococcosis (AE and CE)

Cited by 106 publications

References 192 publications

Immune Exhaustion of T Cells in Alveolar Echinococcosis Patients and Its Reversal by Blocking Checkpoint Receptor TIGIT in a Murine Model

Immune Exhaustion of T Cells in Alveolar Echinococcosis Patients and Its Reversal by Blocking Checkpoint Receptor TIGIT in a Murine Model

Granulomatous responses in larval taeniid infections

Pro-Angiogenic Activity of Monocytic-Type Myeloid-Derived Suppressor Cells from Balb/C Mice Infected with Echinococcus Granulosus and the Regulatory Role of miRNAs

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