The degree of microbiome complexity influences the epithelial response to infection.
The degree of microbiome complexity influences the epithelial response to infection.
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DOI：
10.1186/1471-2164-10-380
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发表时间：
2009-08-18
期刊：
影响因子：
4.4
通讯作者：
Handfield M
中科院分区：
文献类型：
--
作者：
Mans JJ;von Lackum K;Dorsey C;Willis S;Wallet SM;Baker HV;Lamont RJ;Handfield M
人类微生物群落已知极其复杂，但大多数发病机制研究是在单一物种感染模型中进行的。因此，宿主固有菌群的复杂程度是否会影响致病物种的潜在毒力仍不清楚。此外，共生菌的定植是否会影响宿主细胞对致病物种的反应，除了表面受体的直接物理饱和、营养物质的螯合、口腔物理化学环境的调节或细菌素的产生之外，也仍不清楚。我们以口腔上皮细胞为模型，假设致病物种的毒力可能因与宿主细胞相互作用的菌群的复杂性而异。
这是第一份确定上皮细胞对与特定复杂微生物群落共培养的整体转录反应的报告。在我们的模型中，人永生化牙龈角质形成细胞（HIGK）被共生菌和致病菌的单一培养物以及混合培养物感染。被感染细胞的整体转录反应得到了验证，并在表型上得到了确认。在我们的模型中，共生菌能够调节具有广泛生理功能的宿主基因的表达，并在细胞水平上拮抗致病菌的作用。出乎意料的是，共生菌的抑制作用与其抑制致病菌黏附或入侵的能力无关。
研究上皮细胞对单一和复杂微生物挑战的整体转录组，为更好地理解细菌 - 细菌相互作用以及细菌 - 宿主相互作用如何影响宿主的整体反应提供了线索。这项工作提供的证据表明，混合微生物群落的复杂程度确实会影响宿主上皮细胞对感染的转录反应，并对当前关于细菌物种潜在致病性与实际致病性的定论提出了挑战。这些发现支持了这样一种概念，即口腔共生菌群的成员已经进化出细胞机制，可直接调节宿主细胞对致病物种的反应并减弱其相对致病性。
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. 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. 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.
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影响因子：
14.9
作者：
Khatri P;Voichita C;Kattan K;Ansari N;Khatri A;Georgescu C;Tarca AL;Draghici S
通讯作者：
Draghici S
影响因子：
4.3
作者：
Demmer RT;Behle JH;Wolf DL;Handfield M;Kebschull M;Celenti R;Pavlidis P;Papapanou PN
通讯作者：
Papapanou PN
影响因子：
3.4
作者：
Handfield, M;Mans, JJ;Lamont, RJ
通讯作者：
Lamont, RJ
影响因子：
3.1
作者：
Krisanaprakornkit, S;Kimball, JR;Dale, DA
通讯作者：
Dale, DA
影响因子：
14.9
作者：
Draghici, S;Khatri, P;Tainsky, MA
通讯作者：
Tainsky, MA