期刊
PLOS ONE
卷 9, 期 11, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0113080
关键词
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资金
- EU Reintegration Grant [PERG05-GA-2009-249313]
- Universitatsbund Wurzburg
- Deutsche Forschungsgemeinschaft (DFG) [Sonderforschungsbereich 688]
- DFG Individual Grants [RE 3450/3-1, RE 3450/5-1]
- Stiftung Pathobiochemie
- Molekulare Diagnostik
- German Federal Ministry for Education and Research (CTH, Junior Group, TRP A6) [BMBF 01EO1003]
- Center for Thrombosis and Hemostasis (CTH) Doctoral Candidate Fellowship [BMBF 01EO1003]
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 upregulation 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.
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