A helminth-derived suppressor of ST2 blocks allergic responses
The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/54017 |
| _version_ | 1811236799164448768 |
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| author | Francesco Vacca Caroline Chauché Abhishek Jamwal Elizabeth C Hinchy Graham Heieis Holly Webster Adefunke Ogunkanbi Zala Sekne William F Gregory Martin Wear Georgia Perona-Wright Matthew K Higgins Josquin A Nys E Suzanne Cohen Henry J McSorley |
| author_facet | Francesco Vacca Caroline Chauché Abhishek Jamwal Elizabeth C Hinchy Graham Heieis Holly Webster Adefunke Ogunkanbi Zala Sekne William F Gregory Martin Wear Georgia Perona-Wright Matthew K Higgins Josquin A Nys E Suzanne Cohen Henry J McSorley |
| author_sort | Francesco Vacca |
| collection | DOAJ |
| description | The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor. |
| first_indexed | 2024-04-12T12:15:26Z |
| format | Article |
| id | doaj.art-33d967843f4146868a42245249420393 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:15:26Z |
| publishDate | 2020-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-33d967843f4146868a422452494203932022-12-22T03:33:27ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.54017A helminth-derived suppressor of ST2 blocks allergic responsesFrancesco Vacca0https://orcid.org/0000-0001-6808-5221Caroline Chauché1Abhishek Jamwal2Elizabeth C Hinchy3Graham Heieis4Holly Webster5Adefunke Ogunkanbi6Zala Sekne7William F Gregory8Martin Wear9Georgia Perona-Wright10Matthew K Higgins11https://orcid.org/0000-0002-2870-1955Josquin A Nys12E Suzanne Cohen13Henry J McSorley14https://orcid.org/0000-0003-1300-7407Centre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United KingdomCentre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomBioscience Asthma, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United KingdomInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomDivision of Cell Signalling and Immunology, School of Life Sciences, Wellcome Trust Building, University of Dundee, Dundee, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomCentre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United Kingdom; Division of Microbiology & Parasitology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, United KingdomThe Edinburgh Protein Production Facility (EPPF), Wellcome Trust Centre for Cell Biology (WTCCB), University of Edinburgh, Edinburgh, United KingdomInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomBioscience Asthma, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United KingdomBioscience Asthma, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United KingdomCentre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United Kingdom; Division of Cell Signalling and Immunology, School of Life Sciences, Wellcome Trust Building, University of Dundee, Dundee, United KingdomThe IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor.https://elifesciences.org/articles/54017allergyasthmaHelminthparasiteIL-33ST2 |
| spellingShingle | Francesco Vacca Caroline Chauché Abhishek Jamwal Elizabeth C Hinchy Graham Heieis Holly Webster Adefunke Ogunkanbi Zala Sekne William F Gregory Martin Wear Georgia Perona-Wright Matthew K Higgins Josquin A Nys E Suzanne Cohen Henry J McSorley A helminth-derived suppressor of ST2 blocks allergic responses eLife allergy asthma Helminth parasite IL-33 ST2 |
| title | A helminth-derived suppressor of ST2 blocks allergic responses |
| title_full | A helminth-derived suppressor of ST2 blocks allergic responses |
| title_fullStr | A helminth-derived suppressor of ST2 blocks allergic responses |
| title_full_unstemmed | A helminth-derived suppressor of ST2 blocks allergic responses |
| title_short | A helminth-derived suppressor of ST2 blocks allergic responses |
| title_sort | helminth derived suppressor of st2 blocks allergic responses |
| topic | allergy asthma Helminth parasite IL-33 ST2 |
| url | https://elifesciences.org/articles/54017 |
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