دورية أكاديمية
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.
العنوان: | 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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المؤلفون: | Francis IP; Department of Microbiology, Boston University School of Medicine, 72 E. Concord St., Room L504, Boston, MA, 02118, USA., Islam EA; Department of Molecular Genetics, University of Toronto, Room 4383, Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S1A8, Canada., Gower AC; Clinical and Translational Science Institute, Boston University School of Medicine, 715 Albany St. E-727, Boston, MA, 02118, USA., Shaik-Dasthagirisaheb YB; Department of Microbiology, Boston University School of Medicine, 72 E. Concord St., Room L504, Boston, MA, 02118, USA., Gray-Owen SD; Department of Molecular Genetics, University of Toronto, Room 4383, Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S1A8, Canada., Wetzler LM; Department of Medicine, Boston University School of Medicine, 715 Albany St. E-113, Boston, MA, 02118, USA. lwetzler@bu.edu.; Department of Microbiology, Boston University School of Medicine, 72 E. Concord St., Room L504, Boston, MA, 02118, USA. lwetzler@bu.edu. |
المصدر: | BMC genomics [BMC Genomics] 2018 Aug 22; Vol. 19 (1), pp. 627. Date of Electronic Publication: 2018 Aug 22. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 100965258 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2164 (Electronic) Linking ISSN: 14712164 NLM ISO Abbreviation: BMC Genomics Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central, [2000- |
مواضيع طبية MeSH: | Neisseria gonorrhoeae*/immunology , Transcriptome*, Estrous Cycle/*physiology , Gonorrhea/*genetics , Host-Pathogen Interactions/*genetics , Inflammation/*genetics , Reproductive Tract Infections/*genetics, Animals ; Disease Models, Animal ; Estrous Cycle/genetics ; Female ; Gene Expression Profiling ; Gonorrhea/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Inflammation/physiopathology ; Mice ; Microarray Analysis ; Reproductive Tract Infections/immunology ; Reproductive Tract Infections/microbiology |
مستخلص: | Background: 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. Results: 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 identified a diestrus-specific induction of type-1 interferon signaling pathways. Conclusions: 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. |
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معلومات مُعتمدة: | R01 AI103400 United States AI NIAID NIH HHS; T32 AI007309 United States AI NIAID NIH HHS; 2R01AI103400-05 National Institute of Allergy and Infectious Diseases; MOP-15499 Canada Canadian Institutes of Health Research |
فهرسة مساهمة: | Keywords: Disease modeling; Gonorrhea; Host immune response; Microarray; Murine reproductive cycle; Neisseria gonorrhoeae; Transcriptome |
تواريخ الأحداث: | Date Created: 20180824 Date Completed: 20181105 Latest Revision: 20181114 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC6106831 |
DOI: | 10.1186/s12864-018-5000-7 |
PMID: | 30134832 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1471-2164 |
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DOI: | 10.1186/s12864-018-5000-7 |