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The Myeloid Immune Signature of Enterotoxigenic Bacteroides Fragilis-Induced Murine Colon Tumorigenesis
Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of IL-17-dependent colon tumorigenesis in Min(Apc+/-)mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppr...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159334/ https://www.ncbi.nlm.nih.gov/pubmed/27301879 http://dx.doi.org/10.1038/mi.2016.53 |
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author | Orberg, Erik Thiele Fan, Hongni Tam, Ada J. Dejea, Christine M. Destefano-Shields, Christina E. Wu, Shaoguang Chung, Liam Finard, Benjamin B. Wu, Xinqun Fathi, Payam Ganguly, Sudipto Fu, Juan Pardoll, Drew M. Sears, Cynthia L. Housseau, Franck |
author_facet | Orberg, Erik Thiele Fan, Hongni Tam, Ada J. Dejea, Christine M. Destefano-Shields, Christina E. Wu, Shaoguang Chung, Liam Finard, Benjamin B. Wu, Xinqun Fathi, Payam Ganguly, Sudipto Fu, Juan Pardoll, Drew M. Sears, Cynthia L. Housseau, Franck |
author_sort | Orberg, Erik Thiele |
collection | PubMed |
description | Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of IL-17-dependent colon tumorigenesis in Min(Apc+/-)mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), which are known to promote tumorigenesis. The myeloid compartment associated with ETBF-induced colon tumorigenesis in Min mice was defined using flow cytometry and gene expression profiling. Cell sorted immature myeloid cells were functionally assayed for inhibition of T cell proliferation and iNOS expression in order to delineate MDSC populations. A comparison of ETBF infection to that of other oncogenic bacteria (Fusobacterium nucleatum or pks+ E. coli) revealed a specific, ETBF-associated colonic immune infiltrate. ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic (MO)-MDSCs. Combined action of the Bacteroides fragilis enterotoxin BFT and IL-17 on colonic epithelial cells promoted the differentiation of MO-MDSCs, which selectively upregulated Arg1 and Nos2, produced NO and suppressed T cell proliferation. Evidence of a pathogenic inflammatory signature in humans colonized with ETBF may allow for the identification of populations at risk for developing colon cancer. |
format | Online Article Text |
id | pubmed-5159334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-51593342017-03-06 The Myeloid Immune Signature of Enterotoxigenic Bacteroides Fragilis-Induced Murine Colon Tumorigenesis Orberg, Erik Thiele Fan, Hongni Tam, Ada J. Dejea, Christine M. Destefano-Shields, Christina E. Wu, Shaoguang Chung, Liam Finard, Benjamin B. Wu, Xinqun Fathi, Payam Ganguly, Sudipto Fu, Juan Pardoll, Drew M. Sears, Cynthia L. Housseau, Franck Mucosal Immunol Article Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of IL-17-dependent colon tumorigenesis in Min(Apc+/-)mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), which are known to promote tumorigenesis. The myeloid compartment associated with ETBF-induced colon tumorigenesis in Min mice was defined using flow cytometry and gene expression profiling. Cell sorted immature myeloid cells were functionally assayed for inhibition of T cell proliferation and iNOS expression in order to delineate MDSC populations. A comparison of ETBF infection to that of other oncogenic bacteria (Fusobacterium nucleatum or pks+ E. coli) revealed a specific, ETBF-associated colonic immune infiltrate. ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic (MO)-MDSCs. Combined action of the Bacteroides fragilis enterotoxin BFT and IL-17 on colonic epithelial cells promoted the differentiation of MO-MDSCs, which selectively upregulated Arg1 and Nos2, produced NO and suppressed T cell proliferation. Evidence of a pathogenic inflammatory signature in humans colonized with ETBF may allow for the identification of populations at risk for developing colon cancer. 2016-06-15 2017-03 /pmc/articles/PMC5159334/ /pubmed/27301879 http://dx.doi.org/10.1038/mi.2016.53 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Orberg, Erik Thiele Fan, Hongni Tam, Ada J. Dejea, Christine M. Destefano-Shields, Christina E. Wu, Shaoguang Chung, Liam Finard, Benjamin B. Wu, Xinqun Fathi, Payam Ganguly, Sudipto Fu, Juan Pardoll, Drew M. Sears, Cynthia L. Housseau, Franck The Myeloid Immune Signature of Enterotoxigenic Bacteroides Fragilis-Induced Murine Colon Tumorigenesis |
title | The Myeloid Immune Signature of Enterotoxigenic Bacteroides Fragilis-Induced Murine Colon Tumorigenesis |
title_full | The Myeloid Immune Signature of Enterotoxigenic Bacteroides Fragilis-Induced Murine Colon Tumorigenesis |
title_fullStr | The Myeloid Immune Signature of Enterotoxigenic Bacteroides Fragilis-Induced Murine Colon Tumorigenesis |
title_full_unstemmed | The Myeloid Immune Signature of Enterotoxigenic Bacteroides Fragilis-Induced Murine Colon Tumorigenesis |
title_short | The Myeloid Immune Signature of Enterotoxigenic Bacteroides Fragilis-Induced Murine Colon Tumorigenesis |
title_sort | myeloid immune signature of enterotoxigenic bacteroides fragilis-induced murine colon tumorigenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159334/ https://www.ncbi.nlm.nih.gov/pubmed/27301879 http://dx.doi.org/10.1038/mi.2016.53 |
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