عنوان

Novel Mouse Models to Reveal Pathogenic Determinants that Contribute to Gonococcal Infection and Pelvic Inflammatory Disease

Number

TL48698

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Novel Mouse Models to Reveal Pathogenic Determinants that Contribute to Gonococcal Infection and Pelvic Inflammatory Disease

General Material Designation

[Thesis]

First Statement of Responsibility

Epshita Anher Islam

Subsequent Statement of Responsibility

Gray-Owen, Scott D.

Name of Publisher, Distributor, etc.

University of Toronto (Canada)

Date of Publication, Distribution, etc.

2016

Specific Material Designation and Extent of Item

125

Text of Note

Committee members: Anderson, Michele; Dennis, Jim; Navarre, William

Text of Note

Place of publication: United States, Ann Arbor; ISBN=978-1-339-55407-5

Dissertation or thesis details and type of degree

Ph.D.

Discipline of degree

Molecular and Medical Genetics

Body granting the degree

University of Toronto (Canada)

Text preceding or following the note

2016

Text of Note

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.

Microbiology; Immunology

Subject Term

Biological sciences;Health and environmental sciences;Female reproductive cycle;Gonorrhea;Mouse models;Opa-ceacam interactions;Pelvic inflammatory disease

Lee, Yan-Jiun

Gray-Owen, Scott D.

Subdivision

Molecular and Medical Genetics

University of Toronto (Canada)

Call Number

1775730374; 10043954

Electronic name

p

[Thesis]

276903

a

Y