{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:26:18Z","timestamp":1787567178037,"version":"build-2736575974"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K18229"],"award-info":[{"award-number":["JP21K18229"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K21266"],"award-info":[{"award-number":["JP20K21266"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23H02122"],"award-info":[{"award-number":["JP23H02122"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007802","name":"Institute for Fermentation, Osaka","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJSP2108"],"award-info":[{"award-number":["JPMJSP2108"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The intestinal microbiota is essential for maintaining intestinal homeostasis by regulating mucosal immune responses. Identifying bacterial traits that support stable host interactions is therefore crucial for developing next-generation mucosal probiotics. RNase T2 is a conserved ribonuclease with species-specific functions. In Escherichia coli, RNase T2 (RNase I) suppresses biofilm formation, a key process for intestinal colonization. We previously showed that an RNase I-deficient E. coli (\u0394rna) strain stably colonizes the mouse intestine. Here, we analyzed the immunogenic properties of the \u0394rna strain. Heat-killed \u0394rna induced an early IL-1\u03b2 and TNF-\u03b1-skewed cytokine response in RAW264.7 macrophages, with reduced IL-6 expression compared to wild type. In mice, \u0394rna colonization caused no intestinal tissue injury but enhanced IL-6 and IL-22 expression in the cecum and colon. Selected TLR-specific reporter assays identified TLR5-dependent signaling driven by increased FliC expression. These findings show that RNase I deficiency modulates immune activation while maintaining non-pathogenic mucosal interactions.<\/jats:p>","DOI":"10.1093\/bbb\/zbag079","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:21:56Z","timestamp":1780917716000},"page":"1265-1272","source":"Crossref","is-referenced-by-count":0,"title":["Altered flagellin-TLR5 signaling pathway in the interaction between the host and laboratory\u00a0\n                    <i>Escherichia coli<\/i>\n                    strains engineered for enhanced intestinal colonization in mice"],"prefix":"10.1093","volume":"90","author":[{"given":"Tsuyoshi","family":"Tachibana","sequence":"first","affiliation":[{"name":"Department of Veterinary Medical Sciences, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6564-6872","authenticated-orcid":false,"given":"Atsushi","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryutaro","family":"Fukui","sequence":"additional","affiliation":[{"name":"Synergy Institute for Mucosal Vaccine Research and Development, Chiba University , Inohana, Chuo-ku, Chiba ,","place":["Japan"]},{"name":"Medical Mycology Research Center, Chiba University , Inohana, Chuo-ku, Chiba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Tochinai","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Mochizuki","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-7350","authenticated-orcid":false,"given":"Wataru","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]},{"name":"Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3117-4962","authenticated-orcid":false,"given":"Tetsuhiro","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]},{"name":"Collaborative Research Institute for Innovative Microbiology, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5900-1425","authenticated-orcid":false,"given":"Shigeru","family":"Kakuta","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]},{"name":"Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]},{"name":"Collaborative Research Institute for Innovative Microbiology, The University of Tokyo , Yayoi, Bunkyo-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"2026082404521353500_bib1","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1038\/sj.onc.1204178","article-title":"Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27","volume":"20","author":"Acquati","year":"2001","journal-title":"Oncogene"},{"key":"2026082404521353500_bib2","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1093\/intimm\/dxf069","article-title":"Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines","volume":"14","author":"Applequist","year":"2002","journal-title":"Int Immunol"},{"key":"2026082404521353500_bib3","doi-asserted-by":"publisher","first-page":"2006.0008","DOI":"10.1038\/msb4100050","article-title":"Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection","volume":"2","author":"Baba","year":"2006","journal-title":"Mol Syst Biol"},{"key":"2026082404521353500_bib4","doi-asserted-by":"publisher","first-page":"fuae019","DOI":"10.1093\/femsre\/fuae019","article-title":"Mechanisms of host adaptation by bacterial pathogens","volume":"48","author":"Barber","year":"2024","journal-title":"FEMS Microbiol Rev"},{"key":"2026082404521353500_bib5","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.immuni.2017.04.008","article-title":"Homeostatic immunity and the microbiota","volume":"46","author":"Belkaid","year":"2017","journal-title":"Immunity"},{"key":"2026082404521353500_bib6","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41385-018-0061-0","article-title":"Subcellular antigen localization in commensal E. coli is critical for T cell activation and induction of specific tolerance","volume":"12","author":"Bennek","year":"2019","journal-title":"Mucosal Immunol"},{"key":"2026082404521353500_bib7","doi-asserted-by":"publisher","first-page":"10.1128\/ecosalplus.8.3.1.2","DOI":"10.1128\/ecosalplus.8.3.1.2","article-title":"The life of commensal Escherichia coli in the mammalian intestine","volume":"1:","author":"Conway","year":"2004","journal-title":"EcoSal Plus"},{"key":"2026082404521353500_bib8","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1021\/acschembio.0c00390","article-title":"RNase I modulates Escherichia coli motility, metabolism, and resistance","volume":"15","author":"Duggal","year":"2020","journal-title":"ACS Chem Biol"},{"key":"2026082404521353500_bib9","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.2147\/JIR.S407521","article-title":"TLR5 signaling in the regulation of intestinal mucosal immunity","volume":"16","author":"Feng","year":"2023","journal-title":"J Inflamm Res"},{"key":"2026082404521353500_bib10","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1042\/BCJ20170906","article-title":"RNase I regulates Escherichia coli 2\u2019,3\u2019-cyclic nucleotide monophosphate levels and biofilm formation","volume":"475","author":"Fontaine","year":"2018","journal-title":"Biochem J"},{"key":"2026082404521353500_bib11","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1084\/jem.20082316","article-title":"Unc93B1 biases toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing","volume":"206","author":"Fukui","year":"2009","journal-title":"J Exp Med"},{"key":"2026082404521353500_bib12","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.3389\/fimmu.2018.01491","article-title":"Cleavage of toll-like receptor 9 ectodomain is required for in vivo responses to single strand DNA","volume":"9","author":"Fukui","year":"2018","journal-title":"Front Immunol"},{"key":"2026082404521353500_bib13","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1016\/j.cell.2019.11.001","article-title":"TLR8 is a sensor of RNase T2 degradation products","volume":"179","author":"Greulich","year":"2019","journal-title":"Cell"},{"key":"2026082404521353500_bib14","doi-asserted-by":"publisher","first-page":"154","DOI":"10.15252\/embj.201489083","article-title":"Bulk RNA degradation by nitrogen starvation-induced autophagy in yeast","volume":"34","author":"Huang","year":"2015","journal-title":"EMBO J"},{"key":"2026082404521353500_bib15","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat Immunol"},{"key":"2026082404521353500_bib16","doi-asserted-by":"publisher","first-page":"e20192195","DOI":"10.1084\/jem.20192195","article-title":"The role of IL-22 in intestinal health and disease","volume":"217","author":"Keir","year":"2020","journal-title":"J Exp Med"},{"key":"2026082404521353500_bib17","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1002\/eji.201040391","article-title":"IL-6: regulator of Treg\/Th17 balance","volume":"40","author":"Kimura","year":"2010","journal-title":"Eur J Immunol"},{"key":"2026082404521353500_bib18","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.3390\/microorganisms12051026","article-title":"A review of the mechanisms of bacterial colonization of the mammal gut","volume":"12","author":"Lin","year":"2024","journal-title":"Microorganisms"},{"key":"2026082404521353500_bib19","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1093\/intimm\/dxab033","article-title":"Skewed endosomal RNA responses from TLR7 to TLR3 in RNase T2-deficient macrophages","volume":"33","author":"Liu","year":"2021","journal-title":"Int Immunol"},{"key":"2026082404521353500_bib20","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2026082404521353500_bib21","doi-asserted-by":"publisher","first-page":"150448","DOI":"10.1016\/j.bbrc.2024.150448","article-title":"Establishment of the improved colonization of Escherichia coli laboratory strain in the intestine mediated by single gene deletion","volume":"734","author":"Minami","year":"2024","journal-title":"Biochem Biophys Res Commun"},{"key":"2026082404521353500_bib22","doi-asserted-by":"publisher","first-page":"108554","DOI":"10.1016\/j.jbc.2025.108554","article-title":"The ribonuclease RNase T2 mediates selective autophagy of ribosomes induced by starvation in Saccharomyces cerevisiae","volume":"301","author":"Minami","year":"2025","journal-title":"J Biol Chem"},{"key":"2026082404521353500_bib23","doi-asserted-by":"publisher","first-page":"941931","DOI":"10.3389\/fimmu.2022.941931","article-title":"Nucleic acid sensing by toll-like receptors in the endosomal compartment","volume":"13","author":"Miyake","year":"2022","journal-title":"Front Immunol"},{"key":"2026082404521353500_bib24","doi-asserted-by":"publisher","first-page":"15378","DOI":"10.1074\/jbc.M117.791780","article-title":"Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4\/myeloid differentiation factor-2 complex","volume":"292","author":"Okamoto","year":"2017","journal-title":"J Biol Chem"},{"key":"2026082404521353500_bib25","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.immuni.2020.03.009","article-title":"Immune sensing of synthetic, bacterial, and protozoan RNA by toll-like receptor 8 requires coordinated processing by RNase T2 and RNase 2","volume":"52","author":"Ostendorf","year":"2020","journal-title":"Immunity"},{"key":"2026082404521353500_bib26","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.ijmm.2009.03.003","article-title":"Split immune response after oral vaccination of mice with recombinant Escherichia coli Nissle 1917 expressing fimbrial adhesin K88","volume":"299","author":"Remer","year":"2009","journal-title":"Int J Med Microbiol"},{"key":"2026082404521353500_bib27","doi-asserted-by":"publisher","first-page":"1000873","DOI":"10.3389\/fbioe.2022.1000873","article-title":"Microbiome engineering: engineered live biotherapeutic products for treating human disease","volume":"10","author":"Rutter","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"key":"2026082404521353500_bib28","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/s41385-018-0084-6","article-title":"E. coli Nissle 1917 is a safe mucosal delivery vector for a birch-grass pollen chimera to prevent allergic poly-sensitization","volume":"12","author":"Sarate","year":"2019","journal-title":"Mucosal Immunol"},{"key":"2026082404521353500_bib29","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1146\/annurev.arplant.56.032604.144249","article-title":"Self-incompatibility in plants","volume":"56","author":"Takayama","year":"2005","journal-title":"Annu Rev Plant Biol"},{"key":"2026082404521353500_bib30","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.crbiot.2020.03.001","article-title":"Restoration of wild-type motility to flagellin-knockout Escherichia coli by varying promoter, copy number and induction strength in plasmid-based expression of flagellin","volume":"2","author":"Thomson","year":"2020","journal-title":"Curr Res Biotechnol"},{"key":"2026082404521353500_bib31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/imm.12538","article-title":"Microbiota and host immune responses: a love-hate relationship","volume":"147","author":"Tomkovich","year":"2016","journal-title":"Immunology"},{"key":"2026082404521353500_bib32","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1007\/s00535-009-0094-y","article-title":"Immune responses of TLR5(+) lamina propria dendritic cells in enterobacterial infection","volume":"44","author":"Uematsu","year":"2009","journal-title":"J Gastroenterol"},{"key":"2026082404521353500_bib33","doi-asserted-by":"publisher","first-page":"3164","DOI":"10.1002\/eji.200737306","article-title":"Identification of a novel negative role of flagellin in regulating IL-10 production","volume":"37","author":"Vicente-Suarez","year":"2007","journal-title":"Eur J Immunol"},{"key":"2026082404521353500_bib34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3390\/vaccines5040050","article-title":"Adjuvant probiotics and the intestinal microbiome: enhancing vaccines and immunotherapy outcomes","volume":"5","author":"Vitetta","year":"2017","journal-title":"Vaccines (Basel)"},{"key":"2026082404521353500_bib35","doi-asserted-by":"publisher","first-page":"G96","DOI":"10.1152\/ajpgi.00273.2005","article-title":"Flagellin\/TLR5 responses in epithelia reveal intertwined activation of inflammatory and apoptotic pathways","volume":"290","author":"Zeng","year":"2006","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026082404521353500_bib36","doi-asserted-by":"publisher","first-page":"5633403","DOI":"10.1155\/2022\/5633403","article-title":"Next-generation probiotics: microflora intervention to human diseases","volume":"2022","author":"Zhang","year":"2022","journal-title":"Biomed Res Int"}],"container-title":["Bioscience, Biotechnology, and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bbb\/advance-article-pdf\/doi\/10.1093\/bbb\/zbag079\/68501390\/zbag079.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bbb\/article-pdf\/90\/9\/1265\/68501390\/zbag079.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bbb\/article-pdf\/90\/9\/1265\/68501390\/zbag079.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:52:18Z","timestamp":1787561538000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bbb\/article\/90\/9\/1265\/8704723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,6,9]]},"published-print":{"date-parts":[[2026,8,24]]}},"URL":"https:\/\/doi.org\/10.1093\/bbb\/zbag079","relation":{},"ISSN":["1347-6947"],"issn-type":[{"value":"1347-6947","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,6,9]]}}}