|
" Novel Mouse Models to Reveal Pathogenic Determinants that Contribute to Gonococcal Infection and Pelvic Inflammatory Disease "
Epshita Anher Islam
Gray-Owen, Scott D.
| Document Type
|
:
|
Latin Dissertation
|
| Language of Document
|
:
|
English
|
| Record Number
|
:
|
803890
|
| Doc. No
|
:
|
TL48698
|
| Call number
|
:
|
1775730374; 10043954
|
| Main Entry
|
:
|
Lee, Yan-Jiun
|
| Title & Author
|
:
|
Novel Mouse Models to Reveal Pathogenic Determinants that Contribute to Gonococcal Infection and Pelvic Inflammatory Disease\ Epshita Anher IslamGray-Owen, Scott D.
|
| College
|
:
|
University of Toronto (Canada)
|
| Date
|
:
|
2016
|
| Degree
|
:
|
Ph.D.
|
| field of study
|
:
|
Molecular and Medical Genetics
|
| student score
|
:
|
2016
|
| Page No
|
:
|
125
|
| Note
|
:
|
Committee members: Anderson, Michele; Dennis, Jim; Navarre, William
|
| Note
|
:
|
Place of publication: United States, Ann Arbor; ISBN=978-1-339-55407-5
|
| Abstract
|
:
|
Neisseria gonorrhoeae (Ngo) is an obligate human pathogen that causes gonorrhea, one of the most prevalent sexually transmitted infections worldwide. In women, endocervical infections are often asymptomatic; however, bacterial progression into the uterus and oviducts can lead to pelvic inflammatory disease (PID), an umbrella term used to describe a spectrum of inflammatory conditions of the upper genital tract. Although a mouse model for long term colonization of the lower genital tract has been previously established, there has been little consideration of Ngo infections involving the upper genital tract. As a result, host factors that influence disease outcome, which can range from mild discomfort to severe inflammation, pain, reproductive tract scarring and even infertility, remain elusive. My thesis work first aimed to establish a mouse model that can be used to study upper genital tract infection by N. gonorrhoeae. I reveal that the immunopathology associated with ascendant Ngo infections, as well as the development of a humoral response in the long term, are largely determined by the stage of the female reproductive cycle. Next, to examine how gonococcal Opa protein-mediated association with human CEACAM receptor proteins impacts infection and disease, I took advantage of “humanized” transgenic mouse lines that express various combinations of human CEACAMs. I show that CEACAM expression within the female genital tract of mice reflects that seen in humans, and that the spectrum of CEACAMs expressed influences colonization, clearance, and PID symptoms associated with gonococcal infection. Taken together, my findings provide new models to study infection within the genital tract, and use these to provide novel insights regarding factors that affect colonization and disease development.
|
| Subject
|
:
|
Microbiology; Immunology
|
| Descriptor
|
:
|
Biological sciences;Health and environmental sciences;Female reproductive cycle;Gonorrhea;Mouse models;Opa-ceacam interactions;Pelvic inflammatory disease
|
| Added Entry
|
:
|
Gray-Owen, Scott D.
|
| Added Entry
|
:
|
Molecular and Medical GeneticsUniversity of Toronto (Canada)
|
| |