{"doi":"10.1371/journal.pone.0113080","title":"Gut Microbial Colonization Orchestrates TLR2 Expression, Signaling and Epithelial Proliferation in the Small Intestinal Mucosa","abstract":null,"journal":"PLoS ONE","year":2014,"id":673463,"datarank":0.6749714505495399,"base_score":4.499809670330265,"endowment":4.499809670330265,"self_citation_contribution":0.6749714505495399,"citation_network_contribution":0.0,"self_endowment_contribution":0.6749714505495399,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":89,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1759542,"name":"Inês Brandão","orcid":null,"position":1,"is_corresponding":false},{"id":1759543,"name":"Sven Jäckel","orcid":null,"position":2,"is_corresponding":false},{"id":1759544,"name":"Nelli Ens","orcid":null,"position":3,"is_corresponding":false},{"id":1759545,"name":"Maren Lillich","orcid":null,"position":4,"is_corresponding":false},{"id":1738201,"name":"Ulrich Walter","orcid":null,"position":5,"is_corresponding":false},{"id":1322519,"name":"Christoph Reinhardt","orcid":"0000-0001-7002-8533","position":6,"is_corresponding":false},{"id":1759541,"name":"Nives Hörmann","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Gut Microbial Colonization Orchestrates TLR2 Expression, Signaling and Epithelial Proliferation in the Small Intestinal Mucosa","abstract":"The gut microbiota is an environmental factor that determines renewal of the intestinal epithelium and remodeling of the intestinal mucosa. At present, it is not resolved if components of the gut microbiota can augment innate immune sensing in the intestinal epithelium via the up-regulation of Toll-like receptors (TLRs). Here, we report that colonization of germ-free (GF) Swiss Webster mice with a complex gut microbiota augments expression of TLR2. The microbiota-dependent up-regulation of components of the TLR2 signaling complex could be reversed by a 7 day broad-spectrum antibiotic treatment. TLR2 downstream signaling via the mitogen-activated protein kinase (ERK1/2) and protein-kinase B (AKT) induced by bacterial TLR2 agonists resulted in increased proliferation of the small intestinal epithelial cell line MODE-K. Mice that were colonized from birth with a normal gut microbiota (conventionally-raised; CONV-R) showed signs of increased small intestinal renewal and apoptosis compared with GF controls as indicated by elevated mRNA levels of the proliferation markers Ki67 and Cyclin D1, elevated transcripts of the apoptosis marker Caspase-3 and increased numbers of TUNEL-positive cells per intestinal villus structure. In accordance, TLR2-deficient mice showed reduced proliferation and reduced apoptosis. Our findings suggest that a tuned proliferation response of epithelial cells following microbial colonization could aid to protect the host from its microbial colonizers and increase intestinal surface area.","is_dataset_classified":null,"base_score":4.499809670330265,"endowment":4.499809670330265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25396415","pmcid":"PMC4232598","openalex_id":"https://openalex.org/W2018972715","authors":[],"funders":[{"funder_name":"European Commission","grant_id":"249313","title":"Microbial-induced Angiogenesis in the Gut"}],"total_grants":1,"fwci":1.7013,"citation_percentile":0.83706377,"influential_citations":0,"citation_trend":[{"year":2015,"count":1},{"year":2016,"count":9},{"year":2017,"count":4},{"year":2018,"count":11},{"year":2019,"count":10},{"year":2020,"count":12},{"year":2021,"count":22},{"year":2022,"count":6},{"year":2023,"count":6},{"year":2024,"count":4},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0113080&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0113080&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0113080","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0113080","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25396415","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4232598","host_type":"repository"},{"url":"https://doaj.org/article/0cda4ee5ebb24eca9f7169e95bea07e8","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/_Gut_Microbial_Colonization_Orchestrates_TLR2_Expression_Signaling_and_Epithelial_Proliferation_in_the_Small_Intestinal_Mucosa_/1242112","host_type":"repository"},{"url":"https://www.openaccessrepository.it/record/27419","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4232598","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4232598?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pone.0113080","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0113080","host_type":""},{"url":"https://zenodo.org/records/27419","host_type":""},{"url":"https://zenodo.org/record/27419","host_type":""},{"url":"http://europepmc.org/articles/PMC4232598","host_type":""},{"url":"https://doaj.org/toc/1932-6203","host_type":""},{"url":"http://europepmc.org/articles/PMC4232598?pdf=render","host_type":""}],"fields_of_study":["Immune Response and Inflammation","Gut microbiota and health","Helicobacter pylori-related gastroenterology studies","0301 basic medicine","03 medical and health sciences","0303 health sciences","Animals","Apoptosis","Caspase 3","Cell Line","Cell Proliferation","Cyclin D1","Epithelial Cells","Escherichia coli","Intestinal Mucosa","Intestine, Small","Ki-67 Antigen","Lipopeptides","Mice","Mice, Inbred C57BL","Mice, Knockout","Mitogen-Activated Protein Kinase 1","Mitogen-Activated Protein Kinase 3","Proto-Oncogene Proteins c-akt","Signal Transduction","Toll-Like Receptor 2","Toll-Like Receptor 6","Transcriptome","Up-Regulation"],"mesh_terms":["Animals","Cell Line","Epithelial Cells","Escherichia coli","Intestinal Mucosa","Intestine, Small","Mice, Inbred C57BL","Signal Transduction","Up-Regulation","Apoptosis","Mice, Knockout","Ki-67 Antigen","Cyclin D1","Mitogen-Activated Protein Kinase 1","Mitogen-Activated Protein Kinase 3","Cell Proliferation","Proto-Oncogene Proteins c-akt","Toll-Like Receptor 2","Toll-Like Receptor 6","Mice","Caspase 3","Lipopeptides","Transcriptome"],"keywords":["TLR2","Biology","Intestinal mucosa","Intestinal epithelium","Signal transduction","Cell biology","Intestinal villus","Protein kinase B","Gut flora","Innate immune system","Kinase","Epithelium","Microbiology","TLR4","Immunology","Crypt","Immune system","Internal medicine","Endocrinology","Medicine","Physiology","Inflammatory Diseases","Science","Apoptosis","Gastroenterology and Hepatology","Biochemistry","Pediatrics","Cell Line","Lipopeptides","Mice","Toll-like receptor-2, epithelial cells, small intestine, gut microbiota, germ-free, proliferation","Intestine, Small","Medicine and Health Sciences","Escherichia coli","Animals","Cyclin D1","Cell Proliferation","Mice, Knockout","Mitogen-Activated Protein Kinase 1","Mitogen-Activated Protein Kinase 3","Caspase 3","Q","R","Biology and Life Sciences","Epithelial Cells","Toll-Like Receptor 2","Mice, Inbred C57BL","Species Interactions","Ki-67 Antigen","Proto-Oncogene Proteins c-akt","Developmental Biology","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T13:29:37.407127Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}