Distinct transcriptional profiles characterize oral epithelium-microbiota interactions.
Transcriptional profiling, bioinformatics, statistical and ontology tools were used to uncover and dissect genes and pathways of human gingival epithelial cells that are modulated upon interaction with the periodontal pathogens Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Consistent with their biological and clinical differences, the common core transcriptional response of epithelial cells to both organisms was very limited, and organism-specific responses predominated. A large number of differentially regulated genes linked to the P53 apoptotic network were found with both organisms, which was consistent with the pro-apoptotic phenotype observed with A. actinomycetemcomitans and anti-apoptotic phenotype of P. gingivalis. Furthermore, with A. actinomycetemcomitans, the induction of apoptosis did not appear to be Fas- or TNF(alpha)-mediated. Linkage of specific bacterial components to host pathways and networks provided additional insight into the pathogenic process. Comparison of the transcriptional responses of epithelial cells challenged with parental P. gingivalis or with a mutant of P. gingivalis deficient in production of major fimbriae, which are required for optimal invasion, showed major expression differences that reverberated throughout the host cell transcriptome. In contrast, gene ORF859 in A. actinomycetemcomitans, which may play a role in intracellular homeostasis, had a more subtle effect on the transcriptome. These studies help unravel the complex and dynamic interactions between host epithelial cells and endogenous bacteria that can cause opportunistic infections.
Handfield
Martin
M
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA. mhandfield@dental.ufl.edu
Mans
Jeffrey J
JJ
Zheng
Gaolin
G
Lopez
M Cecilia
MC
Mao
Song
S
Progulske-Fox
Ann
A
Narasimhan
Giri
G
Baker
Henry V
HV
Lamont
Richard J
RJ
D016976:Aggregatibacter actinomycetemcomitans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D002460:Cell Line; D018920:Coculture Techniques; D017753:Ecosystem; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D036781:Fimbriae Proteins / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005798:Genes, Bacterial; D005881:Gingiva / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D009061:Mouth Mucosa / Q000378:metabolism / Q000382:microbiology*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013045:Species Specificity; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D016159:Tumor Suppressor Protein p53; C063055:fimbrillin; D036781:Fimbriae Proteins