title: The reproductive cycle is a pathogenic determinant during gonococcal pelvic inflammatory disease in mice.
abstract: Women with asymptomatic Neisseria gonorrhoeae infection are at risk of developing pelvic inflammatory disease (PID) if the bacteria ascend from the endocervix into the uterus and oviducts. Factors that affect disease severity, ranging from mild discomfort to severe inflammation, pain, and infertility, remain elusive. Herein we perform direct transcervical inoculation of N. gonorrhoeae into the uterus of mice to establish an infection that leads to PID. Profoundly different disease outcomes were apparent at different stages of the reproductive cycle. Mice that were infected during the diestrus stage of the reproductive cycle displayed extensive gonococcal penetration into the submucosa, severe inflammation, and clinical signs reflecting discomfort. Meanwhile, infection during the intervening estrus stage showed only modest effects. Furthermore, a gonococcal-specific humoral response was only elicited following the penetrative upper genital tract (UGT) infection during diestrus but not estrus. Strikingly, the potential for antibodies to contribute to protection during re-infection also depends upon the reproductive stage, as antigonococcal antibodies within the genital tract were markedly higher when mice were in diestrus. Combined, this work establishes a robust new model reflecting gonococcal PID in humans and reveals how the reproductive cycle determines the pathogenic outcome of gonococcal infections of the UGT.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: E A
authors.initials: EA
authors.lastname: Islam
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shaik-Dasthagirisaheb
authors.affiliation: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, Michael DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Kaushic
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Wetzler
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: S D
authors.initials: SD
authors.lastname: Gray-Owen
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D058070:Asymptomatic Diseases; D004031:Diestrus / Q000276:immunology*; D004195:Disease Models, Animal; D004971:Estrus / Q000276:immunology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000382:microbiology; D006069:Gonorrhea / Q000276:immunology*; D056724:Immunity, Humoral; D007156:Immunologic Memory; D051379:Mice; D008815:Mice, Inbred Strains; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D000292:Pelvic Inflammatory Disease / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial