Distinct transcriptional profiles characterize oral epithelium-microbiota interactions
Distinct transcriptional profiles characterize oral epithelium-microbiota interactions
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DOI：
10.1111/j.1462-5822.2005.00513.x
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发表时间：
2005-06-01
影响因子：
3.4
通讯作者：
Lamont, RJ
中科院分区：
文献类型：
--
作者：
Handfield, M;Mans, JJ;Lamont, RJ
运用转录图谱分析、生物信息学、统计学和本体论工具，揭示并剖析了人牙龈上皮细胞在与牙周病原体伴放线放线杆菌和牙龈卟啉单胞菌相互作用时发生调节的基因和通路。与它们生物学和临床差异相符的是，上皮细胞对这两种微生物的共同核心转录反应非常有限，而微生物特异性反应占主导。在两种微生物作用下都发现了大量与P53凋亡网络相关的差异调节基因，这与伴放线放线杆菌的促凋亡表型以及牙龈卟啉单胞菌的抗凋亡表型是一致的。此外，对于伴放线放线杆菌，凋亡的诱导似乎不是由Fas或肿瘤坏死因子α介导的。特定细菌成分与宿主通路和网络的关联为致病过程提供了更多的见解。比较用牙龈卟啉单胞菌亲本菌株或缺乏主要菌毛产生的牙龈卟啉单胞菌突变体（菌毛是最佳侵入所必需的）刺激上皮细胞的转录反应，显示出在整个宿主细胞转录组中产生回响的主要表达差异。相比之下，伴放线放线杆菌中的基因ORF859（可能在细胞内稳态中起作用）对转录组的影响更为微妙。这些研究有助于揭示宿主上皮细胞与可引起机会性感染的内源性细菌之间复杂而动态的相互作用。
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 antiapoptotic 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.