Increased Incidence and Characteristics of Alveolar Echinococcosis in Patients With Immunosuppression-Associated Conditions

Chauchet, Adrien; Grenouillet, Frédéric; Dentan, Charlotte; Martino, Vincent Di; Contreras, Remy; Deconinck, Eric; Vuitton, Dominique A.; Vitrat, V.; Bardonnet, Karine; Bartholomot, B.; Isabelle, Beurton-Chataigner; Blagosklonov, Oleg; Bresson‐Hadni, Solange; Pascale, Brientini Marie; Sylvie, Cappelle; Delabrousse, É; Vincent, Di Martino; Evrard, Philippe; Félix, Sophie; Patrick, Giraudoux; Grenouillet, F.; Heyd, Bruno; Valmary‐Degano, Séverine; Knapp, Jenny; Koch, Sarah; Georges, Mantion; Millon, Laurence; Raoul, Francis; Richou, Carine; Claire, Vanlemmens; Angèle, Vuitton Dominique; Vuitton, Lucine; Prost, Patricia; Claire, Godet; Abergel, Armand; Beytout, Jean; Monique, Cambon; François, Besancenot Jean; Bernadette, Cusenier; Hillon, Patrick; Anne, Minello; Odile, Faure; Létoublon, Christian; Dumortier, J; Guillaud, Olivier; Christian, Partensky; Rabodonirina, Méja; Wallon, Martine; Martine, Piarroux; Chatelain, Eric; Johann, M; Jean-Jacques, Raabe; Daniel, Sondag; Gerard, A; Letranchant, L.; Machouart, M.; Watelet, J.; Farges, Olivier; Didier, S.; Chemla, Cathy; Francois, Delattre Jean; Guérin, B; Debruyne, Monique; Abou-Bacar, Ahmed; Audet, Maxime; Hansmann, Yves; Lefèbvre, Nicolas; Li, Veronique; Blandine, Alby-Lepresle

doi:10.1093/cid/ciu520

Cited by 121 publications

(118 citation statements)

References 29 publications

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“…It is well established that T cell–mediated cellular immunity, especially that mediated by CD4 + T cells, is critical for mounting a granulomatous inflammatory response and achieving resistance against E. multilocularis infection, and is highly associated with abortive or slow progression of the metacestode in AE patients . Conversely, functional impairment of T cells from these patients is associated with enhanced establishment and growth of the metacestode . We confirmed that not only CD4 + T cells but also CD8 + T cells were involved in controlling metacestode growth in our model.…”

Section: Discussionsupporting

confidence: 81%

“…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.…”

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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: Discussionsupporting

confidence: 81%

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confidence: 99%

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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“…For those individuals where infection leads to disease, the developing parasite is partially controlled by host immunity: in the case of immunocompetence, a slowly growing metacestode is observed, referring to that form of AE where first clinical signs appear years after infection. In the case of impaired immunity, caused by AIDS, other immunodeficiencies or immunosuppressing therapies such as following organ transplantation, cancer chemotherapy, or chronic inflammatory diseases, an uncontrolled proliferation of the metacestode is observed, leading to a more rapidly progressing disease status (Chauchet et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Susceptibility versus resistance in alveolar echinococcosis (larval infection with Echinococcus multilocularis)

Gottstein

Wang

Boubaker

et al. 2015

Veterinary Parasitology

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Epidemiological studies have demonstrated that the majority of human individuals exposed to infection with Echinococcus spp. eggs exhibit resistance to disease as shown by either seroconversion to parasite--specific antigens, and/or the presence of 'dying out' or 'aborted' metacestodes, not including hereby those individuals who putatively got infected but did not seroconvert and who subsequently allowed no development of the pathogen. For those individuals where infection leads to disease, the developing parasite is partially controlled by host immunity. In infected humans, the type of immune response developed by the host accounts for the subsequent trichotomy concerning the parasite development: (i) seroconversion proving infection, but lack of any hepatic lesion indicating the failure of the parasite to establish and further develop within the liver; or resistance as shown by the presence of fully calcified lesions; (ii) controlled susceptibility as found in the "conventional" alveolar echinococcosis (AE) patients who experience clinical signs and symptoms approximately 5-15 years after infection, and (iii) uncontrolled hyperproliferation of the metacestode due to an impaired immune response (AIDS or other immunodeficiencies). Immunomodulation of host immunity toward anergy seems to be triggered by parasite metabolites. Beside immunomodulating IL-10, TGFβ-driven regulatory T cells have been shown to play a crucial role in the parasite-modulated progressive course of AE. A novel CD4+CD25+ Treg effector molecule FGL2 recently yielded new insight into the tolerance process in Echinococcus multilocularis infection.

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“…The chronic nature of CE and AE and a strong reliance on advanced imaging for diagnosis continues to impact the speed of case detection in socioeconomically disadvantaged communities. Occurrence of AE as an opportunistic infection in patients with therapeutic immune suppression may have worrisome consequences in the near future [3, 15]. Going forward, control will continue to rely on taking a One Health approach, involving physicians, veterinarians, ecologists, social scientists, laboratory scientists, and others.…”

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confidence: 99%

Cystic and alveolar echinococcosis: Successes and continuing challenges

et al. 2017

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Increased Incidence and Characteristics of Alveolar Echinococcosis in Patients With Immunosuppression-Associated Conditions

Abstract: Patients with immunosuppression are at increased risk for occurrence, delayed diagnosis, and progression of AE.

Cited by 121 publications

References 29 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

Susceptibility versus resistance in alveolar echinococcosis (larval infection with Echinococcus multilocularis)

Cystic and alveolar echinococcosis: Successes and continuing challenges

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