Multi-species oral biofilm promotes reconstructed human gingiva epithelial barrier function

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作者
Lin Shang
Dongmei Deng
Jeroen Kees Buskermolen
Marleen Marga Janus
Bastiaan Philip Krom
Sanne Roffel
Taco Waaijman
Cor van Loveren
Wim Crielaard
Susan Gibbs
机构
[1] University of Amsterdam and Vrije Universiteit Amsterdam,Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA)
[2] University of Amsterdam and Vrije Universiteit Amsterdam,Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA)
[3] Amsterdam UMC,Department of Molecular Cell Biology and Immunology
[4] Vrije Universiteit Amsterdam,undefined
来源
Scientific Reports | / 8卷
关键词
Human Gingiva; Elafin; Adrenomedullin (ADM); Biofilm Exposure; Host-microbiome Interactions;
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摘要
Since the oral mucosa is continuously exposed to abundant microbes, one of its most important defense features is a highly proliferative, thick, stratified epithelium. The cellular mechanisms responsible for this are still unknown. The aim of this study was to determine whether multi-species oral biofilm contribute to the extensive stratification and primed antimicrobial defense in epithelium. Two in vitro models were used: 3D reconstructed human gingiva (RHG) and oral bacteria representative of multi-species commensal biofilm. The organotypic RHG consists of a reconstructed stratified gingiva epithelium on a gingiva fibroblast populated hydrogel (lamina propria). Biofilm was cultured from healthy human saliva, and consists of typical commensal genera Granulicatella and major oral microbiota genera Veillonella and Streptococcus. Biofilm was applied topically to RHG and host–microbiome interactions were studied over 7 days. Compared to unexposed RHG, biofilm exposed RHG showed increased epithelial thickness, more organized stratification and increased keratinocyte proliferation. Furthermore biofilm exposure increased production of RHG anti-microbial proteins Elafin, HBD2 and HBD3 but not HBD1, adrenomedullin or cathelicidin LL-37. Inflammatory and antimicrobial cytokine secretion (IL-6, CXCL8, CXCL1, CCL20) showed an immediate and sustained increase. In conclusion, exposure of RHG to commensal oral biofilm actively contributes to RHG epithelial barrier function.
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