title: Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract, but Is Not Required for Infection in a Novel Male Murine Rectal Infection Model.
abstract: Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due to the asymptomatic nature of these infections. Women suffer from numerous complications from chronic chlamydial infections, which include pelvic inflammatory disease and infertility. We previously demonstrated in culture that host cell nectin-1 knockdown significantly reduced chlamydial titers and inclusion size. Here, we sought to determine whether nectin-1 was required for chlamydial development in vivo by intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring chlamydial shedding by chlamydial titer assay. We observed a significant reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin-1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical staining in mouse cervical tissue confirmed that there are fewer chlamydial inclusions in Chlamydia-infected nectin-1-/- mice. Notably, anorectal chlamydial infections are becoming a substantial health burden, though little is known regarding the pathogenesis of these infections. We therefore established a novel male murine model of rectal chlamydial infection, which we used to determine whether nectin-1 is required for anorectal chlamydial infection in male mice. In contrast to the data from vaginal infection, no difference in rectal chlamydial shedding was observed when male nectin-1+/+ and nectin-1-/- mice were compared. Through the use of these two models, we have demonstrated that nectin-1 promotes chlamydial infection in the female genital tract but does not appear to contribute to rectal infection in male mice. These models could be used to further characterize tissue and sex related differences in chlamydial infection.
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Slade
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Jennifer V
authors.initials: JV
authors.lastname: Hall
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kintner
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Regenia
authors.initials: R
authors.lastname: Phillips-Campbell
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Schoborg
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002690:Chlamydia Infections / Q000235:genetics*; D023502:Chlamydia muridarum / Q000254:growth & development / Q000472:pathogenicity; D002692:Chlamydia trachomatis / Q000254:growth & development / Q000472:pathogenicity; D005260:Female; D020022:Genetic Predisposition to Disease; D005831:Genital Diseases, Female / Q000235:genetics* / Q000382:microbiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000075983:Nectins; D012002:Rectal Diseases / Q000235:genetics* / Q000382:microbiology; D060737:Reproductive Tract Infections / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins