Publication:
Endogenous IL-33 Accelerates Metacestode Growth during Late-Stage Alveolar Echinococcosis.

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dc.contributor.authorAutier, Brice
dc.contributor.authorManuel, Christelle
dc.contributor.authorLundström Stadelmann, Britta
dc.contributor.authorGirard, Jean-Philippe
dc.contributor.authorGottstein, Bruno
dc.contributor.authorGangneux, Jean-Pierre
dc.contributor.authorSamson, Michel
dc.contributor.authorRobert-Gangneux, Florence
dc.contributor.authorDion, Sarah
dc.date.accessioned2024-10-15T09:48:07Z
dc.date.available2024-10-15T09:48:07Z
dc.date.issued2023-02-14
dc.description.abstractDuring the course of the infectious disease alveolar echinococcosis (AE), the larval stage of Echinococcus multilocularis develops in the liver, where an initial Th1/Th17 immune response may allow its elimination in resistant individuals. In patients susceptible to infection and disease, the Th2 response initiates later, inducing tolerance to the parasite. The role of interleukin 33 (IL-33), an alarmin released during necrosis and known to drive a Th2 immune response, has not yet been described during AE. Wild-type (WT) and IL-33-/- C57BL/6J mice were infected by peritoneal inoculation with E. multilocularis metacestodes and euthanized 4 months later, and their immune response were analyzed. Immunofluorescence staining and IL-33 enzyme-linked immunosorbent assay (ELISA) were also performed on liver samples from human patients with AE. Overall, metacestode lesions were smaller in IL-33-/- mice than in WT mice. IL-33 was detected in periparasitic tissues, but not in mouse or human serum. In infected mice, endogenous IL-33 modified peritoneal macrophage polarization and cytokine profiles. Th2 cytokine concentrations were positively correlated with parasite mass in WT mice, but not in IL-33-/- mice. In human AE patients, IL-33 concentrations were higher in parasitic tissues than in distant liver parenchyma. The main sources of IL-33 were CD31+ endothelial cells of the neovasculature, present within lymphoid periparasitic infiltrates together with FOXP3+ Tregs. In the murine model, periparasitic IL-33 correlated with accelerated parasite growth putatively through the polarization of M2-like macrophages and release of immunosuppressive cytokines IL-10 and transforming growth factor β1 (TGF-β1). We concluded that IL-33 is a key alarmin in AE that contributes to the tolerogenic effect of systemic Th2 cytokines. IMPORTANCE Infection with the metacestode stage of Echinococcus multilocularis, known as alveolar echinococcosis, is the most severe cestodosis worldwide. However, less than 1% of exposed individuals, in which the immune system is unable to control the parasite, develop the disease. The factors responsible for this interindividual variability are not fully understood. In this in vivo study comparing wild-type and IL-33-/- infected mice, together with data from human clinical samples, we determined that IL-33, an alarmin released following tissue injury and involved in the pathogenesis of cancer and asthma, accelerates the progression of the disease by modulating the periparasitic microenvironment. This suggests that targeting IL-33 could be of interest for the management of patients with AE, and that IL-33 polymorphisms could be responsible for increased susceptibility to AE.
dc.description.sponsorshipInstitut für Parasitologie (IPA)
dc.description.sponsorshipInstitut für Infektionskrankheiten (IFIK) - Parasitology
dc.identifier.doi10.48350/178819
dc.identifier.pmid36786637
dc.identifier.publisherDOI10.1128/spectrum.04239-22
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/121627
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofMicrobiology spectrum
dc.relation.issn2165-0497
dc.relation.organizationDCD5A442BD12E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442BFE6E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C1CCE17DE0405C82790C4DE2
dc.subjectEchinococcus multilocularis IL-1RL1 IL-33 ST2 alveolar echinococcosis angiogenesis
dc.subject.ddc500 - Science::570 - Life sciences; biology
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.subject.ddc600 - Technology::630 - Agriculture
dc.titleEndogenous IL-33 Accelerates Metacestode Growth during Late-Stage Alveolar Echinococcosis.
dc.typearticle
dspace.entity.typePublication
dspace.file.typetext
oaire.citation.issue2
oaire.citation.startPagee0423922
oaire.citation.volume11
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oairecerif.author.affiliationInstitut für Parasitologie (IPA)
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oairecerif.author.affiliationInstitut für Infektionskrankheiten (IFIK) - Parasitology
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oairecerif.author.affiliation2Institut für Infektionskrankheiten (IFIK)
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unibe.date.licenseChanged2023-02-16 14:29:36
unibe.description.ispublishedinpress
unibe.eprints.legacyId178819
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unibe.subtype.articlejournal

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