title: Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection.
abstract: The growing popularity of levonorgestrel (LNG)-releasing intra-uterine systems for long-acting reversible contraception provides strong impetus to define immunomodulatory properties of this exogenous progestin. In initial in vitro studies herein, we found LNG significantly impaired activation of human dendritic cell (DCs) and their capacity to promote allogeneic T cell proliferation. In follow-up studies in a murine model of intranasal Chlamydia trachomatis infection, we analogously found that LNG treatment prior to infection dramatically reduced CD40 expression in DCs isolated from draining lymph nodes at 2 days post infection (dpi). At 12 dpi, we also detected significantly fewer CD4+and CD8+T cells in the lungs of LNG-treated mice. This inhibition of DC activation and T cell expansion in LNG-treated mice also delayed chlamydial clearance and the resolution of pulmonary inflammation. Conversely, administering agonist anti-CD40 monoclonal antibody to LNG-treated mice at 1 dpi restored lung T cell numbers and chlamydial burden at 12 dpi to levels seen in infected controls. Together, these studies reveal that LNG suppresses DC activation and function, and inhibits formation of pathogen-specific T cell immunity. They also highlight the need for studies that define in vivo effects of LNG use on human host response to microbial pathogens.
authors.affiliation: Department of Microbial infection &Immunity, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
authors.forename: Nirk E
authors.initials: NE
authors.lastname: Quispe Calla
authors.affiliation: Department of Microbial infection &Immunity, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
authors.forename: Rodolfo D
authors.initials: RD
authors.lastname: Vicetti Miguel
authors.affiliation: Department of Microbial infection &Immunity, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
authors.forename: Ao
authors.initials: A
authors.lastname: Mei
authors.affiliation: Department of Microbial infection &Immunity, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
authors.forename: Shumin
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Microbial infection &Immunity, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
authors.forename: Jocelyn R
authors.initials: JR
authors.lastname: Gilmore
authors.affiliation: Department of Microbial infection &Immunity, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.|Department of Obstetrics &Gynecology The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Cherpes
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002690:Chlamydia Infections / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000502:physiology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D016912:Levonorgestrel / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D016912:Levonorgestrel