The UPR sensor IRE1α promotes dendritic cell responses to control Toxoplasma gondii infection
| العنوان: | The UPR sensor IRE1α promotes dendritic cell responses to control Toxoplasma gondii infection |
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| المؤلفون: | Jamal Khalife, Sofie Rennen, Eik Hoffmann, Sophie Janssens, Nicolas Blanchard, Véronique Peucelle, Sabrina Marion, Ludovic Huot, Victor Bosteels, Sandra Maréchal, Anaïs F Poncet, Sylia Chehade |
| المساهمون: | Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Universiteit Gent = Ghent University [Belgium] (UGENT), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), SM has been supported by the Laboratoire d’Excellence (LabEx) ParaFrap from the National Agency for Research ANR-11-LABX-0024 grant and a joint Chaire d’Excellence from Université of Lille and the Centre National pour la Recherche Scientifique (CNRS). SJ is a recipient of an ERC Consolidator Grant (Grant Number 819314), several FWO program grants and an EOS grant (G0G7318N). VB is holder of an FWO PhD Fellowship and SR received a PhD BOF grant from the University of Ghent., ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Khalife, Jamal, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID |
| المصدر: | EMBO reports EMBO Reports EMBO Reports, EMBO Press, 2021, 22 (3), pp.e49617. ⟨10.15252/embr.201949617⟩ EMBO REPORTS EMBO Rep EMBO Reports, 2021, 22 (3), pp.e49617. ⟨10.15252/embr.201949617⟩ |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Antigen presentation, Toxoplasma gondii, UPR, Protein Serine-Threonine Kinases, Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Immunity, Endoribonucleases, Genetics, Medicine and Health Sciences, Animals, dendritic cells, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, ATF6, Biology and Life Sciences, Articles, Dendritic cell, biology.organism_classification, cytokines, 3. Good health, antigen presentation, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Immunology, Unfolded Protein Response, Cytokine secretion, Toxoplasma, Toxoplasmosis, 030217 neurology & neurosurgery |
| الوصف: | The unfolded protein response (UPR) has emerged as a central regulator of immune cell responses in several pathologic contexts including infections. However, how intracellular residing pathogens modulate the UPR in dendritic cells (DCs) and thereby affect T cell-mediated immunity remains uncharacterized. Here, we demonstrate that infection of DCs with Toxoplasma gondii (T. gondii) triggers a unique UPR signature hallmarked by the MyD88-dependent activation of the IRE1 alpha pathway and the inhibition of the ATF6 pathway. Induction of XBP1s controls pro-inflammatory cytokine secretion in infected DCs, while IRE1 alpha promotes MHCI antigen presentation of secreted parasite antigens. In mice, infection leads to a specific activation of the IRE1 alpha pathway, which is restricted to the cDC1 subset. Mice deficient for IRE1 alpha and XBP1 in DCs display a severe susceptibility to T. gondii and succumb during the acute phase of the infection. This early mortality is correlated with increased parasite burden and a defect in splenic T-cell responses. Thus, we identify the IRE1 alpha/XBP1s branch of the UPR as a key regulator of host defense upon T. gondii infection. |
| وصف الملف: | application/pdf |
| تدمد: | 1469-221X 1469-3178 |
| DOI: | 10.15252/embr.201949617 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f5ddc742d09015322d9cc4b63868540b |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f5ddc742d09015322d9cc4b63868540b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1469221X 14693178 |
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| DOI: | 10.15252/embr.201949617 |