Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains
Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promo...
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Veröffentlicht in: | PLoS biology 2019-06, Vol.17 (6), p.e3000334-e3000334 |
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creator | Steimle, Alex Menz, Sarah Bender, Annika Ball, Brianna Weber, Alexander N R Hagemann, Thomas Lange, Anna Maerz, Jan K Parusel, Raphael Michaelis, Lena Schäfer, Andrea Yao, Hans Löw, Hanna-Christine Beier, Sina Tesfazgi Mebrhatu, Mehari Gronbach, Kerstin Wagner, Samuel Voehringer, David Schaller, Martin Fehrenbacher, Birgit Autenrieth, Ingo B Oelschlaeger, Tobias A Frick, Julia-Stefanie |
description | Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients. |
doi_str_mv | 10.1371/journal.pbio.3000334 |
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Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.3000334</identifier><identifier>PMID: 31206517</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Bacteria ; Biology and Life Sciences ; Bone marrow ; Border patrol ; CD11c antigen ; Colitis ; Colitis - chemically induced ; Colitis - immunology ; Commensalism ; Cytokines ; Dendritic cells ; Dermatology ; Dextran ; Disease Models, Animal ; E coli ; Ecology and Environmental Sciences ; Escherichia coli ; Escherichia coli - genetics ; Escherichia coli - metabolism ; Escherichia coli Infections - microbiology ; Escherichia coli Proteins - genetics ; Female ; Flagellin ; Flagellin - genetics ; Flagellin - metabolism ; Homeostasis ; Hospitals ; Hygiene ; Immune system ; Immunogenicity ; Infections ; Inflammatory bowel disease ; Inflammatory bowel diseases ; Interleukins ; Intestinal Mucosa ; Intestine ; Intestines ; Lamina propria ; Male ; Medical innovations ; Medical treatment ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Microbiota ; Neutrophils ; Physiological aspects ; Properties (attributes) ; Proteins ; Research and Analysis Methods ; Signal Transduction - immunology ; Sodium ; Sodium sulfate ; Strains (organisms) ; Supervision ; Symbiosis - genetics ; Symbiosis - physiology ; Toll-Like Receptor 5 - metabolism ; Toll-like receptors</subject><ispartof>PLoS biology, 2019-06, Vol.17 (6), p.e3000334-e3000334</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Steimle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Steimle et al 2019 Steimle et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c695t-98d8d5eb1cf395cde30d2df7a5edc2d5f102f3bb2b0dc60bccf3e4c5becea9ff3</citedby><cites>FETCH-LOGICAL-c695t-98d8d5eb1cf395cde30d2df7a5edc2d5f102f3bb2b0dc60bccf3e4c5becea9ff3</cites><orcidid>0000-0003-1808-3556 ; 0000-0002-2532-1922 ; 0000-0001-8157-162X ; 0000-0002-8230-4256 ; 0000-0002-7662-7956</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597123/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597123/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31206517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Teixeira, Luis</contributor><creatorcontrib>Steimle, Alex</creatorcontrib><creatorcontrib>Menz, Sarah</creatorcontrib><creatorcontrib>Bender, Annika</creatorcontrib><creatorcontrib>Ball, Brianna</creatorcontrib><creatorcontrib>Weber, Alexander N R</creatorcontrib><creatorcontrib>Hagemann, Thomas</creatorcontrib><creatorcontrib>Lange, Anna</creatorcontrib><creatorcontrib>Maerz, Jan K</creatorcontrib><creatorcontrib>Parusel, Raphael</creatorcontrib><creatorcontrib>Michaelis, Lena</creatorcontrib><creatorcontrib>Schäfer, Andrea</creatorcontrib><creatorcontrib>Yao, Hans</creatorcontrib><creatorcontrib>Löw, Hanna-Christine</creatorcontrib><creatorcontrib>Beier, Sina</creatorcontrib><creatorcontrib>Tesfazgi Mebrhatu, Mehari</creatorcontrib><creatorcontrib>Gronbach, Kerstin</creatorcontrib><creatorcontrib>Wagner, Samuel</creatorcontrib><creatorcontrib>Voehringer, David</creatorcontrib><creatorcontrib>Schaller, Martin</creatorcontrib><creatorcontrib>Fehrenbacher, Birgit</creatorcontrib><creatorcontrib>Autenrieth, Ingo B</creatorcontrib><creatorcontrib>Oelschlaeger, Tobias A</creatorcontrib><creatorcontrib>Frick, Julia-Stefanie</creatorcontrib><title>Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.</description><subject>Animals</subject><subject>Bacteria</subject><subject>Biology and Life Sciences</subject><subject>Bone marrow</subject><subject>Border patrol</subject><subject>CD11c antigen</subject><subject>Colitis</subject><subject>Colitis - chemically induced</subject><subject>Colitis - immunology</subject><subject>Commensalism</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Dermatology</subject><subject>Dextran</subject><subject>Disease Models, Animal</subject><subject>E coli</subject><subject>Ecology and Environmental Sciences</subject><subject>Escherichia coli</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - metabolism</subject><subject>Escherichia coli Infections - microbiology</subject><subject>Escherichia coli Proteins - genetics</subject><subject>Female</subject><subject>Flagellin</subject><subject>Flagellin - genetics</subject><subject>Flagellin - metabolism</subject><subject>Homeostasis</subject><subject>Hospitals</subject><subject>Hygiene</subject><subject>Immune system</subject><subject>Immunogenicity</subject><subject>Infections</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Interleukins</subject><subject>Intestinal Mucosa</subject><subject>Intestine</subject><subject>Intestines</subject><subject>Lamina propria</subject><subject>Male</subject><subject>Medical innovations</subject><subject>Medical treatment</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiota</subject><subject>Neutrophils</subject><subject>Physiological aspects</subject><subject>Properties (attributes)</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Signal Transduction - immunology</subject><subject>Sodium</subject><subject>Sodium sulfate</subject><subject>Strains (organisms)</subject><subject>Supervision</subject><subject>Symbiosis - genetics</subject><subject>Symbiosis - physiology</subject><subject>Toll-Like Receptor 5 - metabolism</subject><subject>Toll-like receptors</subject><issn>1545-7885</issn><issn>1544-9173</issn><issn>1545-7885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVk1trFDEUxwdRbK1-A9EBX_Rh11x3Mi9CKa0uFAveXkMmOZlNySRrMlvcb2_WnZau9EHJQ8LJ7_zPjVNVLzGaY9rg99dxk4Ly83Xn4pwihChlj6pjzBmfNULwx_feR9WznK8RIqQl4ml1RDFBC46b48pceNWD9y7Uq-0a0o1KTnUe6gS9i6E2MEIaXIBc5-1QQo1O1-sUCzq6Yoy21nEYIGTl6_OsV5CcXjlVrN7VeUzKhfy8emKVz_Biuk-q7xfn384-zS6vPi7PTi9netHycdYKIwyHDmtLW64NUGSIsY3iYDQx3GJELO060iGjF6jThQOmeQcaVGstPale73XXPmY5NShLQrhoWs7bphDLPWGiupbr5AaVtjIqJ_8YYuqlKoVpD5JwRYRpGg2CsQVTQqtGMc6t7nCrNCtaH6Zom24oGUIo1foD0cOf4FayjzdyUTLBhBaBt5NAij83kEc5uKzLMFSAuNnlzYggLSe8oG_-Qh-ubqJ6VQpwwcYSV-9E5SlvOeKciR01f4Aqx8DgdAxgXbEfOLw7cCjMCL_GXm1ylsuvX_6D_fzv7NWPQ5btWZ1izgnsXZ8xkrt9uG2I3O2DnPahuL26P6M7p9sFoL8Bmk0Jbg</recordid><startdate>20190617</startdate><enddate>20190617</enddate><creator>Steimle, Alex</creator><creator>Menz, Sarah</creator><creator>Bender, Annika</creator><creator>Ball, Brianna</creator><creator>Weber, Alexander N R</creator><creator>Hagemann, Thomas</creator><creator>Lange, Anna</creator><creator>Maerz, Jan K</creator><creator>Parusel, Raphael</creator><creator>Michaelis, Lena</creator><creator>Schäfer, Andrea</creator><creator>Yao, Hans</creator><creator>Löw, Hanna-Christine</creator><creator>Beier, Sina</creator><creator>Tesfazgi Mebrhatu, Mehari</creator><creator>Gronbach, Kerstin</creator><creator>Wagner, Samuel</creator><creator>Voehringer, David</creator><creator>Schaller, Martin</creator><creator>Fehrenbacher, Birgit</creator><creator>Autenrieth, Ingo B</creator><creator>Oelschlaeger, Tobias A</creator><creator>Frick, Julia-Stefanie</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PATMY</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><scope>CZG</scope><orcidid>https://orcid.org/0000-0003-1808-3556</orcidid><orcidid>https://orcid.org/0000-0002-2532-1922</orcidid><orcidid>https://orcid.org/0000-0001-8157-162X</orcidid><orcidid>https://orcid.org/0000-0002-8230-4256</orcidid><orcidid>https://orcid.org/0000-0002-7662-7956</orcidid></search><sort><creationdate>20190617</creationdate><title>Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains</title><author>Steimle, Alex ; Menz, Sarah ; Bender, Annika ; Ball, Brianna ; Weber, Alexander N R ; Hagemann, Thomas ; Lange, Anna ; Maerz, Jan K ; Parusel, Raphael ; Michaelis, Lena ; Schäfer, Andrea ; Yao, Hans ; Löw, Hanna-Christine ; Beier, Sina ; Tesfazgi Mebrhatu, Mehari ; Gronbach, Kerstin ; Wagner, Samuel ; Voehringer, David ; Schaller, Martin ; Fehrenbacher, Birgit ; Autenrieth, Ingo B ; Oelschlaeger, Tobias A ; Frick, Julia-Stefanie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c695t-98d8d5eb1cf395cde30d2df7a5edc2d5f102f3bb2b0dc60bccf3e4c5becea9ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Bacteria</topic><topic>Biology and Life Sciences</topic><topic>Bone marrow</topic><topic>Border patrol</topic><topic>CD11c antigen</topic><topic>Colitis</topic><topic>Colitis - chemically induced</topic><topic>Colitis - immunology</topic><topic>Commensalism</topic><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Dermatology</topic><topic>Dextran</topic><topic>Disease Models, Animal</topic><topic>E coli</topic><topic>Ecology and Environmental Sciences</topic><topic>Escherichia coli</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - metabolism</topic><topic>Escherichia coli Infections - microbiology</topic><topic>Escherichia coli Proteins - genetics</topic><topic>Female</topic><topic>Flagellin</topic><topic>Flagellin - genetics</topic><topic>Flagellin - metabolism</topic><topic>Homeostasis</topic><topic>Hospitals</topic><topic>Hygiene</topic><topic>Immune system</topic><topic>Immunogenicity</topic><topic>Infections</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory bowel diseases</topic><topic>Interleukins</topic><topic>Intestinal Mucosa</topic><topic>Intestine</topic><topic>Intestines</topic><topic>Lamina propria</topic><topic>Male</topic><topic>Medical innovations</topic><topic>Medical treatment</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiota</topic><topic>Neutrophils</topic><topic>Physiological aspects</topic><topic>Properties (attributes)</topic><topic>Proteins</topic><topic>Research and Analysis Methods</topic><topic>Signal Transduction - immunology</topic><topic>Sodium</topic><topic>Sodium sulfate</topic><topic>Strains (organisms)</topic><topic>Supervision</topic><topic>Symbiosis - genetics</topic><topic>Symbiosis - physiology</topic><topic>Toll-Like Receptor 5 - metabolism</topic><topic>Toll-like receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Steimle, Alex</creatorcontrib><creatorcontrib>Menz, Sarah</creatorcontrib><creatorcontrib>Bender, Annika</creatorcontrib><creatorcontrib>Ball, Brianna</creatorcontrib><creatorcontrib>Weber, Alexander N R</creatorcontrib><creatorcontrib>Hagemann, Thomas</creatorcontrib><creatorcontrib>Lange, Anna</creatorcontrib><creatorcontrib>Maerz, Jan K</creatorcontrib><creatorcontrib>Parusel, Raphael</creatorcontrib><creatorcontrib>Michaelis, Lena</creatorcontrib><creatorcontrib>Schäfer, Andrea</creatorcontrib><creatorcontrib>Yao, Hans</creatorcontrib><creatorcontrib>Löw, Hanna-Christine</creatorcontrib><creatorcontrib>Beier, Sina</creatorcontrib><creatorcontrib>Tesfazgi Mebrhatu, Mehari</creatorcontrib><creatorcontrib>Gronbach, Kerstin</creatorcontrib><creatorcontrib>Wagner, Samuel</creatorcontrib><creatorcontrib>Voehringer, David</creatorcontrib><creatorcontrib>Schaller, Martin</creatorcontrib><creatorcontrib>Fehrenbacher, Birgit</creatorcontrib><creatorcontrib>Autenrieth, Ingo B</creatorcontrib><creatorcontrib>Oelschlaeger, Tobias A</creatorcontrib><creatorcontrib>Frick, Julia-Stefanie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Steimle, Alex</au><au>Menz, Sarah</au><au>Bender, Annika</au><au>Ball, Brianna</au><au>Weber, Alexander N R</au><au>Hagemann, Thomas</au><au>Lange, Anna</au><au>Maerz, Jan K</au><au>Parusel, Raphael</au><au>Michaelis, Lena</au><au>Schäfer, Andrea</au><au>Yao, Hans</au><au>Löw, Hanna-Christine</au><au>Beier, Sina</au><au>Tesfazgi Mebrhatu, Mehari</au><au>Gronbach, Kerstin</au><au>Wagner, Samuel</au><au>Voehringer, David</au><au>Schaller, Martin</au><au>Fehrenbacher, Birgit</au><au>Autenrieth, Ingo B</au><au>Oelschlaeger, Tobias A</au><au>Frick, Julia-Stefanie</au><au>Teixeira, Luis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2019-06-17</date><risdate>2019</risdate><volume>17</volume><issue>6</issue><spage>e3000334</spage><epage>e3000334</epage><pages>e3000334-e3000334</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31206517</pmid><doi>10.1371/journal.pbio.3000334</doi><orcidid>https://orcid.org/0000-0003-1808-3556</orcidid><orcidid>https://orcid.org/0000-0002-2532-1922</orcidid><orcidid>https://orcid.org/0000-0001-8157-162X</orcidid><orcidid>https://orcid.org/0000-0002-8230-4256</orcidid><orcidid>https://orcid.org/0000-0002-7662-7956</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1545-7885 |
ispartof | PLoS biology, 2019-06, Vol.17 (6), p.e3000334-e3000334 |
issn | 1545-7885 1544-9173 1545-7885 |
language | eng |
recordid | cdi_plos_journals_2258795597 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central |
subjects | Animals Bacteria Biology and Life Sciences Bone marrow Border patrol CD11c antigen Colitis Colitis - chemically induced Colitis - immunology Commensalism Cytokines Dendritic cells Dermatology Dextran Disease Models, Animal E coli Ecology and Environmental Sciences Escherichia coli Escherichia coli - genetics Escherichia coli - metabolism Escherichia coli Infections - microbiology Escherichia coli Proteins - genetics Female Flagellin Flagellin - genetics Flagellin - metabolism Homeostasis Hospitals Hygiene Immune system Immunogenicity Infections Inflammatory bowel disease Inflammatory bowel diseases Interleukins Intestinal Mucosa Intestine Intestines Lamina propria Male Medical innovations Medical treatment Medicine and Health Sciences Mice Mice, Inbred C57BL Microbiota Neutrophils Physiological aspects Properties (attributes) Proteins Research and Analysis Methods Signal Transduction - immunology Sodium Sodium sulfate Strains (organisms) Supervision Symbiosis - genetics Symbiosis - physiology Toll-Like Receptor 5 - metabolism Toll-like receptors |
title | Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains |
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