The degree of microbiome complexity influences the epithelial response to infection Export

@article{citeulike:5486884, abstract = {BACKGROUND:The human microflora is known to be extremely complex, yet most pathogenesis research is conducted in mono-species models of infection. Consequently, it remains unclear whether the level of complexity of a host's indigenous flora can affect the virulence potential of pathogenic species. Furthermore, it remains unclear whether the colonization by commensal species affects a host cell's response to pathogenic species beyond the direct physical saturation of surface receptors, the sequestration of nutrients, the modulation of the physico-chemical environment in the oral cavity, or the production of bacteriocins. Using oral epithelial cells as a model, we hypothesized that the virulence of pathogenic species may vary depending on the complexity of the flora that interacts with host cells.RESULTS:This is the first report that determines the global epithelial transcriptional response to co-culture with defined complex microbiota. In our model, human immortalized gingival keratinocytes (HIGK) were infected with mono- and mixed cultures of commensal and pathogenic species. The global transcriptional response of infected cells was validated and confirmed phenotypically. In our model, commensal species were able to modulate the expression of host genes with a broad diversity of physiological functions and antagonize the effect of pathogenic species at the cellular level. Unexpectedly, the inhibitory effect of commensal species was not correlated with its ability to inhibit adhesion or invasion by pathogenic species.CONCLUSION:Studying the global transcriptome of epithelial cells to single and complex microbial challenges offers clues towards a better understanding of how bacteria-bacteria interactions and bacteria-host interactions impact the overall host response. This work provides evidence that the degree of complexity of a mixed microbiota does influence the transcriptional response to infection of host epithelial cells, and challenges the current dogma regarding the potential versus the actual pathogenicity of bacterial species. These findings support the concept that members of the commensal oral flora have evolved cellular mechanisms that directly modulate the host cell's response to pathogenic species and dampen their relative pathogenicity.}, author = {Mans, Jeffrey and von Lackum, Kate and Dorsey, Cassandra and Willis, Shaun and Wallet, Shannon and Baker, Henry and Lamont, Richard and Handfield, Martin}, citeulike-article-id = {5486884}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2164-10-380}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19689803}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19689803}, doi = {10.1186/1471-2164-10-380}, issn = {1471-2164}, journal = {BMC Genomics}, keywords = {expression, gene, host, interaction, microbiome}, number = {1}, pages = {380+}, posted-at = {2009-10-05 17:00:01}, priority = {2}, title = {The degree of microbiome complexity influences the epithelial response to infection}, url = {http://dx.doi.org/10.1186/1471-2164-10-380}, volume = {10}, year = {2009} }

TY - JOUR ID - citeulike:5486884 L3 - citeulike-article-id:5486884 N2 - BACKGROUND:The human microflora is known to be extremely complex, yet most pathogenesis research is conducted in mono-species models of infection. Consequently, it remains unclear whether the level of complexity of a host's indigenous flora can affect the virulence potential of pathogenic species. Furthermore, it remains unclear whether the colonization by commensal species affects a host cell's response to pathogenic species beyond the direct physical saturation of surface receptors, the sequestration of nutrients, the modulation of the physico-chemical environment in the oral cavity, or the production of bacteriocins. Using oral epithelial cells as a model, we hypothesized that the virulence of pathogenic species may vary depending on the complexity of the flora that interacts with host cells.RESULTS:This is the first report that determines the global epithelial transcriptional response to co-culture with defined complex microbiota. In our model, human immortalized gingival keratinocytes (HIGK) were infected with mono- and mixed cultures of commensal and pathogenic species. The global transcriptional response of infected cells was validated and confirmed phenotypically. In our model, commensal species were able to modulate the expression of host genes with a broad diversity of physiological functions and antagonize the effect of pathogenic species at the cellular level. Unexpectedly, the inhibitory effect of commensal species was not correlated with its ability to inhibit adhesion or invasion by pathogenic species.CONCLUSION:Studying the global transcriptome of epithelial cells to single and complex microbial challenges offers clues towards a better understanding of how bacteria-bacteria interactions and bacteria-host interactions impact the overall host response. This work provides evidence that the degree of complexity of a mixed microbiota does influence the transcriptional response to infection of host epithelial cells, and challenges the current dogma regarding the potential versus the actual pathogenicity of bacterial species. These findings support the concept that members of the commensal oral flora have evolved cellular mechanisms that directly modulate the host cell's response to pathogenic species and dampen their relative pathogenicity. IS - 1 JF - BMC Genomics SN - 1471-2164 TI - The degree of microbiome complexity influences the epithelial response to infection VL - 10 SP - 380 KW - expression KW - gene KW - host KW - interaction KW - microbiome AU - Mans, Jeffrey AU - von Lackum, Kate AU - Dorsey, Cassandra AU - Willis, Shaun AU - Wallet, Shannon AU - Baker, Henry AU - Lamont, Richard AU - Handfield, Martin PY - 2009/// UR - http://dx.doi.org/10.1186/1471-2164-10-380 ER -