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
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PROVIDER: PRJNA454686 | ENA |
REPOSITORIES: ENA
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Project description: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.
2018-08-27 | GSE113962 | GEO
Project description:BackgroundThe 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.ResultsGenes 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 identified a diestrus-specific induction of type-1 interferon signaling pathways.ConclusionsThis 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.
| S-EPMC6106831 | biostudies-literature
Project description:Comparing gene expression in Oral and genital lichen planus with normal oral and genital epithelium trying to idenitfy differently expressed genes in lichen planus compared to normal epithelium Total RNA obtained from oral and genital lichen planus epithelium compared with normal oral and genital epithelium
2013-11-08 | E-GEOD-52130 | biostudies-arrayexpress
Project description:Comparing gene expression in Oral and genital lichen planus with normal oral and genital epithelium trying to idenitfy differently expressed genes in lichen planus compared to normal epithelium
2013-11-08 | GSE52130 | GEO
Project description:To gain insights into the role of androgen in genital morphogenesis, we compared basal transcriptional patterns in genital fibroblasts from 46,XY individuals with either wild-type AR or germline inactivation of the AR as a result of mutation. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
2005-12-21 | GSE3872 | GEO
Project description:To gain insights into the role of androgen in genital morphogenesis, we compared basal transcriptional patterns in genital fibroblasts from 46,XY individuals with either wild-type AR or germline inactivation of the AR as a result of mutation. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Computed
2005-12-20 | E-GEOD-3872 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE3871: Effects of androgen treatment on genital fibroblasts GSE3872: Baseline gene transcription in genital fibroblasts Abstract: BACKGROUND: Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation. RESULTS: Using DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR. CONCLUSIONS: The results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development. Refer to individual Series
2006-03-06 | E-GEOD-4353 | biostudies-arrayexpress
Project description:Bovine genital campylobacteriosis (BGC) is a globally important venereal disease of cattle caused by Campylobacter fetus subspecies (C. fetus) venerealis. Diagnosis of BGC is highly challenging due to the lack of accurate diagnostic tests. To characterise the immune biomarkers for C. fetus venerealis infection, a total of twelve six cycling heifers were selected and categorised as vaccinated (n=6) with Vibrovax® (Zoetis™) and unvaccinated (n=6). All heifers were oestrous synchronised with a double dose of prostaglandin (PGF2) 11 days apart and when in oestrous intravaginally challenged with 2.7x109 CFU live C. fetus venerealis. Relative abundances of serum proteins were calculated using sequential window acquisition of all theoretical fragment ion spectra coupled to tandem mass spectrometry (SWATH-MS) for all heifers at three timepoints: pre-challenge, post-challenge and post-recovery.
2024-10-17 | PXD052863 | Pride
Project description:Abstract: BACKGROUND: Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation. RESULTS: Using DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR. CONCLUSIONS: The results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development. This SuperSeries is composed of the SubSeries listed below.
2006-03-07 | GSE4353 | GEO