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Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression

Trichuris suis ova (TSO) have been tested for therapeutic application in inflammatory bowel diseases (IBD) yet understanding of the underlying mechanisms and safety in an immunocompromised host is limited due to lack of a suitable animal model. We used a recently established rabbit model of dextran...

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Autores principales: Leonardi, Irina, Gerstgrasser, Alexandra, Schmidt, Thomas S. B., Nicholls, Flora, Tewes, Bernhard, Greinwald, Roland, von Mering, Christian, Rogler, Gerhard, Frey-Wagner, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705695/
https://www.ncbi.nlm.nih.gov/pubmed/29184071
http://dx.doi.org/10.1038/s41598-017-16287-4
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author Leonardi, Irina
Gerstgrasser, Alexandra
Schmidt, Thomas S. B.
Nicholls, Flora
Tewes, Bernhard
Greinwald, Roland
von Mering, Christian
Rogler, Gerhard
Frey-Wagner, Isabelle
author_facet Leonardi, Irina
Gerstgrasser, Alexandra
Schmidt, Thomas S. B.
Nicholls, Flora
Tewes, Bernhard
Greinwald, Roland
von Mering, Christian
Rogler, Gerhard
Frey-Wagner, Isabelle
author_sort Leonardi, Irina
collection PubMed
description Trichuris suis ova (TSO) have been tested for therapeutic application in inflammatory bowel diseases (IBD) yet understanding of the underlying mechanisms and safety in an immunocompromised host is limited due to lack of a suitable animal model. We used a recently established rabbit model of dextran sodium sulphate (DSS) induced colitis to study the efficacy, mechanisms and safety of TSO therapy in immunocompetent and immunosuppressed animals. TSO treatment prevented the DSS induced weight loss, delayed the onset of DSS induced symptoms by 2 days and significantly reduced the disease activity (DAI). TSO treatment protected caecal histology and prevented the colitis-associated loss in faecal microbiota diversity. Mainly the transcriptome of lamina propria mononuclear cells (LPMC) was affected by TSO treatment, showing dampened innate and adaptive inflammatory responses. The protective effect of TSO was lost in immunosuppressed rabbits, where TSO exacerbated colitis. Our data show that preventive TSO treatment ameliorates colitis severity in immunocompetent rabbits, modulates LPMC immune responses and reduces faecal dysbiosis. In contrast, the same TSO treatment exacerbates colitis in immunosuppressed animals. Our data provide further evidence for a therapeutic effect of TSO in IBD, yet caution is required with regard to TSO treatment in immunosuppressed patients.
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spelling pubmed-57056952017-12-05 Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression Leonardi, Irina Gerstgrasser, Alexandra Schmidt, Thomas S. B. Nicholls, Flora Tewes, Bernhard Greinwald, Roland von Mering, Christian Rogler, Gerhard Frey-Wagner, Isabelle Sci Rep Article Trichuris suis ova (TSO) have been tested for therapeutic application in inflammatory bowel diseases (IBD) yet understanding of the underlying mechanisms and safety in an immunocompromised host is limited due to lack of a suitable animal model. We used a recently established rabbit model of dextran sodium sulphate (DSS) induced colitis to study the efficacy, mechanisms and safety of TSO therapy in immunocompetent and immunosuppressed animals. TSO treatment prevented the DSS induced weight loss, delayed the onset of DSS induced symptoms by 2 days and significantly reduced the disease activity (DAI). TSO treatment protected caecal histology and prevented the colitis-associated loss in faecal microbiota diversity. Mainly the transcriptome of lamina propria mononuclear cells (LPMC) was affected by TSO treatment, showing dampened innate and adaptive inflammatory responses. The protective effect of TSO was lost in immunosuppressed rabbits, where TSO exacerbated colitis. Our data show that preventive TSO treatment ameliorates colitis severity in immunocompetent rabbits, modulates LPMC immune responses and reduces faecal dysbiosis. In contrast, the same TSO treatment exacerbates colitis in immunosuppressed animals. Our data provide further evidence for a therapeutic effect of TSO in IBD, yet caution is required with regard to TSO treatment in immunosuppressed patients. Nature Publishing Group UK 2017-11-28 /pmc/articles/PMC5705695/ /pubmed/29184071 http://dx.doi.org/10.1038/s41598-017-16287-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Leonardi, Irina
Gerstgrasser, Alexandra
Schmidt, Thomas S. B.
Nicholls, Flora
Tewes, Bernhard
Greinwald, Roland
von Mering, Christian
Rogler, Gerhard
Frey-Wagner, Isabelle
Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression
title Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression
title_full Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression
title_fullStr Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression
title_full_unstemmed Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression
title_short Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression
title_sort preventive trichuris suis ova (tso) treatment protects immunocompetent rabbits from dss colitis but may be detrimental under conditions of immunosuppression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705695/
https://www.ncbi.nlm.nih.gov/pubmed/29184071
http://dx.doi.org/10.1038/s41598-017-16287-4
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