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| Status |
Public on Aug 27, 2018 |
| Title |
Murine host response to Neisseria gonorrhoeae upper genital tract infection reveals a common transcriptional signature, plus distinct inflammatory responses that vary between reproductive cycle phases |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The emergence of fully antimicrobial resistant Neisseria gonorrhoeae has led global public health agencies to identify a critical need for next generation anti-gonococcal pharmaceuticals. The development and success of these compounds will rely upon valid pre-clinical models of gonorrhoeae infection. We recently developed and reported the first model of upper genital tract gonococcal infection. During initial characterization, we observed significant reproductive cycle-based variation in infection outcome. When uterine infection occurred in the diestrus phase, there was significantly greater pathology than during estrus phase. The aim of this study was to evaluate transcriptional profiles of infected uterine tissue from mice in either estrus or diestrus phase in order to elucidate possible mechanisms for these differences. Genes and biological pathways with phase-independent induction during infection showed a chemokine dominant cytokine response to Neisseria gonorrhoeae. Despite general induction being phase-independent, this common anti-gonococcal response demonstrated greater induction during diestrus phase infection. Greater activity of granulocyte adhesion and diapedesis regulators during diestrus infection, particularly in chemokines and diapedesis regulators, was also shown. In addition to a greater induction of the common anti-gonococcal response, Gene Set Enrichment Analysis (GSEA) identified a diestrus-specific induction of type-1 interferon signaling pathways. This transcriptional analysis of murine uterine gonococcal infection during distinct points in the natural reproductive cycle provided evidence for a common anti-gonococcal response characterized by significant induction of granulocyte chemokine expression and high proinflammatory mediators. The basic biology of this host response to N. gonorrhoeae in estrus and diestrus is similar at the pathway level, but varies drastically in magnitude. Overlaying this, we observed type-1 interferon induction specifically in diestrus infection where greater pathology is observed. This supports recent work suggesting this pathway has a significant, possibly host-detrimental, function in gonococcal infection. Together these findings lay the groundwork for further examination of the role of interferons in gonococcal infection. Additionally, this work enables the implementation of the diestrus uterine infection model using the newly characterized host response as a marker of pathology and its prevention as a correlate of candidate vaccine efficacy and ability to protect against the devastating consequences of N. gonorrhoeae-associated sequelae.
Murine microarrays were used to examine transcriptional differences underlying significantly different phenotypes associated with uterine N. gonorrhoeae infection in the estrus versus diestrus phases of the natural reproductive cycle.
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| Overall design |
For each animal in the study, tissue was extracted 6 hours after treatment, mRNA was extracted from whole-organ lysate and run on a single array (1 array per animal). Four animals and arrays were run in each of the infected estrus, infected diestrus, and PBS treated diestrus experimental groups. Three aninals and arrays were run for the PBS treated estrus experimental group.
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| Contributor(s) |
Francis IP, Wetzler LM |
| Citation(s) |
30134832 |
| Submission date |
May 02, 2018 |
| Last update date |
Jun 25, 2019 |
| Contact name |
Boston University Microarray and Sequencing Resource |
| E-mail(s) |
msrdata@bu.edu
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| Organization name |
Boston University
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| Department |
Microarray and Sequencing Resource
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| Street address |
72 East Concord Street, E631
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
| GPL17791 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [mogene20st_Mm_ENTREZG_17.1.0] |
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| Samples (15)
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| GSM3124773 |
Sample 4, estrus phase, infected |
| GSM3124774 |
Sample 5, estrus phase, infected |
| GSM3124775 |
Sample 6, estrus phase, infected |
| GSM3124776 |
Sample 7, estrus phase, infected |
| GSM3124777 |
Sample 12, diestrus phase, uninfected |
| GSM3124778 |
Sample 13, diestrus phase, uninfected |
| GSM3124779 |
Sample 14, diestrus phase, uninfected |
| GSM3124780 |
Sample 15, diestrus phase, uninfected |
| GSM3124781 |
Sample 16, diestrus phase, infected |
| GSM3124782 |
Sample 17, diestrus phase, infected |
| GSM3124783 |
Sample 18, diestrus phase, infected |
| GSM3124784 |
Sample 19, diestrus phase, infected |
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| Relations |
| BioProject |
PRJNA454686 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113962_RAW.tar |
132.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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