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Specific Binding to Differentially Expressed Human Carcinoembryonic Antigenrelated Cell Adhesion Molecules Determines the Outcome of Neisseria Gonorrhoeae Infections Along the Female Reproductive Tract Publisher Pubmed



Islam EA1 ; Anipindi VC2 ; Francis I3 ; Shaikdasthagirisaheb Y3 ; Xu S1 ; Leung N1 ; Sintsova A1 ; Amin M1, 4 ; Kaushic C2 ; Wetzler LM3 ; Grayowen SD1
Authors
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Authors Affiliations
  1. 1. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
  2. 2. Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, Michael DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, ON, Canada
  3. 3. Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, United States
  4. 4. Department of Drug and Food Control, Faculty of Pharmacyand the Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran

Source: Infection and Immunity Published:2018


Abstract

The gonococcal Opa proteins are an antigenically variable family of surface adhesins that bind human carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), CEACAM3, CEACAM5, and/or CEACAM6, cell surface glycoproteins that are differentially expressed on a broad spectrum of human cells and tissues. While they are presumed to be important for infection, the significance of various Opa-CEACAM-mediated cellular interactions in the context of the genital tract has remained unclear. Here, we observed that CEACAM1 and CEACAM5 are differentially expressed on epithelia lining the upper and lower portions of the human female genital tract, respectively. Using transgenic mouse lines expressing human CEACAMs in a manner that reflects this differential pattern, we considered the impact of Opa-CEACAM interactions during uncomplicated lower genital tract infections versus during pelvic inflammatory disease. Our results demonstrate that Opa- CEACAM5 binding on vaginal epithelia facilitates the long-term colonization of the lower genital tract, while Opa protein binding to CEACAM1 on uterine epithelia enhances gonococcal association and penetration into these tissues. While these Opadependent interactions with CEACAM-expressing epithelial surfaces promote infection, Opa binding by neutrophil-expressed CEACAMs counterbalances this by facilitating more effective gonococcal clearance. Furthermore, during uterine infections, CEACAM-dependent tissue invasion aggravates disease pathology by increasing the acute inflammatory response. Together, these findings demonstrate that the outcome of infection is determined by both the cell type-specific expression of human CEACAMs and the CEACAM specificity of the Opa variants expressed, which combine to determine the level of gonococcal association with the genital mucosa versus the extent of CEACAM-dependent inflammation and gonococcal clearance by neutrophils. © 2018 American Society for Microbiology.