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Published on: February 13, 2013
Time-course Transcriptomics Reveals the Impact of Treponema pallidum on Microvascular Endothelial Cell Function and
Abstract:
Syphilis, caused by Treponema pallidum subsp. pallidum, is an urgent global public health threat. Syphilis vaccine development has been impeded by limited understanding of the molecular mechanisms that enable T. pallidum to establish and maintain infection. The vascular endothelium is critical for T. pallidum attachment, dissemination, and host immune response initiation; however, the molecular details of T. pallidum -endothelial interactions are incompletely understood. To enhance understanding, we performed time-course transcriptomic profiling on T. pallidum -exposed brain microvascular endothelial cells. These analyses showed T. pallidum exposure altered pathways related to extracellular matrix, growth factors, integrins, and Rho GTPases. The induced transcriptional response was consistent with endothelial to mesenchymal transition, a process involved in fetal development and vascular dysfunction. This study provides a comprehensive understanding of the molecular responses of endothelial cells to T. pallidum and identified the host pathways that might cause syphilis disease symptoms, information that could aid in syphilis vaccine design.
Highlights:
□ Exposure of microvascular endothelial cells to Treponema pallidum subsp. Pallidum significantly alters the endothelial cell transcriptome □ Signaling pathways related to extracellular matrix organization, growth factors, integrins, and Rho GTPases were overrepresented for genes differentially expressed in T. pallidum -exposed endothelial cells □ Exposure to T. pallidum induces pathways and factors consistent with endothelial to mesenchymal transition, a host process central to development that may explain the devastating effects of congenital infection □ T. pallidum exposure induces expression of Snail, the main transcription factor associated with the process of endothelial to mesenchymal transition.
Insights
Syphilis infection alters endothelial cell gene expression, revealing pathways like endothelial to mesenchymal transition. This finding offers insights into disease mechanisms and potential syphilis vaccine development.
Area of Science:
- Microbiology
- Vascular Biology
- Immunology
Background:
- Syphilis, caused by Treponema pallidum, is a significant global health concern.
- Understanding T. pallidum's interaction with the vascular endothelium is crucial for developing effective treatments and vaccines.
- Current knowledge of molecular interactions between T. pallidum and endothelial cells is limited.
Purpose of the Study:
- To investigate the molecular responses of brain microvascular endothelial cells upon exposure to T. pallidum.
- To identify host pathways involved in T. pallidum infection and disease pathogenesis.
- To provide data that may aid in the design of a syphilis vaccine.
Main Methods:
- Time-course transcriptomic profiling of T. pallidum-exposed brain microvascular endothelial cells.
- Analysis of gene expression alterations and pathway enrichment.
- Identification of key transcription factors involved in the cellular response.
Main Results:
- T. pallidum exposure significantly altered the endothelial cell transcriptome.
- Key affected pathways include those related to extracellular matrix, growth factors, integrins, and Rho GTPases.
- The transcriptional response indicated an induction of endothelial to mesenchymal transition (EMT), including increased Snail expression.
Conclusions:
- T. pallidum significantly impacts endothelial cell molecular pathways, including those associated with EMT.
- These identified host pathways may contribute to syphilis disease symptoms, particularly in congenital cases.
- Understanding these host-pathogen interactions is vital for advancing syphilis vaccine development.
