Intestinal Colonization by Candida albicans Alters Inflammatory Responses in Bruton's Tyrosine Kinase-Deficient Mice
The commensal yeast Candida albicans is part of the human intestinal microflora and is considered a “pathobiont”, a resident microbe with pathogenic potential yet harmless under normal conditions. The aim of this study was to investigate the effect of C. albicans on inflammation of the intestinal tr...
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Public Library of Science
2016
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| Online Access: | http://hdl.handle.net/1721.1/105875 https://orcid.org/0000-0002-7577-4612 https://orcid.org/0000-0002-1090-6071 |
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| author | Strijbis, Karin Dougan, Stephanie K. Esteban, Alexandre Gröne, Andrea Kumamoto, Carol A. Yilmaz, Omer Ploegh, Hidde |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Strijbis, Karin Dougan, Stephanie K. Esteban, Alexandre Gröne, Andrea Kumamoto, Carol A. Yilmaz, Omer Ploegh, Hidde |
| author_sort | Strijbis, Karin |
| collection | MIT |
| description | The commensal yeast Candida albicans is part of the human intestinal microflora and is considered a “pathobiont”, a resident microbe with pathogenic potential yet harmless under normal conditions. The aim of this study was to investigate the effect of C. albicans on inflammation of the intestinal tract and the role of Bruton's tyrosine kinase (Btk). Btk is an enzyme that modulates downstream signaling of multiple receptors involved in innate and adaptive immunity, including the major anti-fungal receptor Dectin-1. Colitis was induced in wild type and Btk-/- mice by treatment with dextran sodium sulfate (DSS) and the gastrointestinal tract of selected treatment groups were then colonized with C. albicans. Colonization by C. albicans neither dampened nor exacerbated inflammation in wild type mice, but colon length and spleen weight were improved in Btk-deficient mice colonized with C. albicans. Neutrophil infiltration was comparable between wild type and Btk-/- mice, but the knockout mice displayed severely reduced numbers of macrophages in the colon during both DSS and DSS/Candida treatment. Smaller numbers and reduced responsiveness of Btk-/- macrophages might partially explain the improved colon length of Btk-/- mice as a result of Candida colonization. Surprisingly, DSS/Candida-treated Btk-/- animals had higher levels of certain pro-inflammatory cytokines and levels of the anti-inflammatory cytokine TGF-β were reduced compared to wild type. A clustering and correlation analysis showed that for wild type animals, spleen TGF-β and colon IL-10 and for Btk-/- spleen and colon levels of IL-17A best correlated with the inflammatory parameters. We conclude that in Btk-/- immunocompromised animals, colonization of the gastrointestinal tract by the commensal yeast C. albicans alters inflammatory symptoms associated with colitis. |
| first_indexed | 2024-09-23T15:42:28Z |
| format | Article |
| id | mit-1721.1/105875 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:42:28Z |
| publishDate | 2016 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/1058752022-10-02T03:34:46Z Intestinal Colonization by Candida albicans Alters Inflammatory Responses in Bruton's Tyrosine Kinase-Deficient Mice Strijbis, Karin Dougan, Stephanie K. Esteban, Alexandre Gröne, Andrea Kumamoto, Carol A. Yilmaz, Omer Ploegh, Hidde Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Yilmaz, Omer Ploegh, Hidde The commensal yeast Candida albicans is part of the human intestinal microflora and is considered a “pathobiont”, a resident microbe with pathogenic potential yet harmless under normal conditions. The aim of this study was to investigate the effect of C. albicans on inflammation of the intestinal tract and the role of Bruton's tyrosine kinase (Btk). Btk is an enzyme that modulates downstream signaling of multiple receptors involved in innate and adaptive immunity, including the major anti-fungal receptor Dectin-1. Colitis was induced in wild type and Btk-/- mice by treatment with dextran sodium sulfate (DSS) and the gastrointestinal tract of selected treatment groups were then colonized with C. albicans. Colonization by C. albicans neither dampened nor exacerbated inflammation in wild type mice, but colon length and spleen weight were improved in Btk-deficient mice colonized with C. albicans. Neutrophil infiltration was comparable between wild type and Btk-/- mice, but the knockout mice displayed severely reduced numbers of macrophages in the colon during both DSS and DSS/Candida treatment. Smaller numbers and reduced responsiveness of Btk-/- macrophages might partially explain the improved colon length of Btk-/- mice as a result of Candida colonization. Surprisingly, DSS/Candida-treated Btk-/- animals had higher levels of certain pro-inflammatory cytokines and levels of the anti-inflammatory cytokine TGF-β were reduced compared to wild type. A clustering and correlation analysis showed that for wild type animals, spleen TGF-β and colon IL-10 and for Btk-/- spleen and colon levels of IL-17A best correlated with the inflammatory parameters. We conclude that in Btk-/- immunocompromised animals, colonization of the gastrointestinal tract by the commensal yeast C. albicans alters inflammatory symptoms associated with colitis. 2016-12-19T19:48:43Z 2016-12-19T19:48:43Z 2014-11 2014-07 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/105875 Strijbis, Karin et al. “Intestinal Colonization by Candida Albicans Alters Inflammatory Responses in Bruton’s Tyrosine Kinase-Deficient Mice.” Ed. David R. Andes. PLoS ONE 9.11 (2014): e112472. https://orcid.org/0000-0002-7577-4612 https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1371/journal.pone.0112472 PLoS ONE Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Public Library of Science PLoS |
| spellingShingle | Strijbis, Karin Dougan, Stephanie K. Esteban, Alexandre Gröne, Andrea Kumamoto, Carol A. Yilmaz, Omer Ploegh, Hidde Intestinal Colonization by Candida albicans Alters Inflammatory Responses in Bruton's Tyrosine Kinase-Deficient Mice |
| title | Intestinal Colonization by Candida albicans Alters Inflammatory Responses in Bruton's Tyrosine Kinase-Deficient Mice |
| title_full | Intestinal Colonization by Candida albicans Alters Inflammatory Responses in Bruton's Tyrosine Kinase-Deficient Mice |
| title_fullStr | Intestinal Colonization by Candida albicans Alters Inflammatory Responses in Bruton's Tyrosine Kinase-Deficient Mice |
| title_full_unstemmed | Intestinal Colonization by Candida albicans Alters Inflammatory Responses in Bruton's Tyrosine Kinase-Deficient Mice |
| title_short | Intestinal Colonization by Candida albicans Alters Inflammatory Responses in Bruton's Tyrosine Kinase-Deficient Mice |
| title_sort | intestinal colonization by candida albicans alters inflammatory responses in bruton s tyrosine kinase deficient mice |
| url | http://hdl.handle.net/1721.1/105875 https://orcid.org/0000-0002-7577-4612 https://orcid.org/0000-0002-1090-6071 |
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