Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection

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 hum...

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Bibliographic Details
Published in:Scientific reports 2016-11, Vol.6 (1), p.37723-37723, Article 37723
Main Authors: Quispe Calla, Nirk E., Vicetti Miguel, Rodolfo D., Mei, Ao, Fan, Shumin, Gilmore, Jocelyn R., Cherpes, Thomas L.
Format: Article
Language:English
Subjects:
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Chlamydia
Dendritic cells
Humanities and Social Sciences
Immunity
Immunology
Infections
Lymph nodes
Lymphocytes
Lymphocytes T
multidisciplinary
Pathogens
Rodents
Science
Sexually transmitted diseases
STD
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep37723