Dendritic cell function and pathogen-specific T cell immunity
are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia
trachomatis infection
Nirk E. Quispe Calla, Rodolfo D. Vicetti Miguel, Ao
Mei, Shumin Fan, Jocelyn R. Gilmore & Thomas L. Cherpes
1. Department of Microbial
infection &Immunity, The Ohio State University College of Medicine,
Columbus, OH, 43210, USA.
2. Department of Obstetrics
&Gynecology The Ohio State University College of Medicine, Columbus, OH,
43210, USA.
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.
Scientific Reports. 2016 Nov
28;6:37723. doi: 10.1038/srep37723.
https://www.nature.com/articles/srep37723Md. Rodolfo D. Vicetti Miguel, Ex-Miembro del GII
Md. Nirk E. Quispe Calla, Past President del GII
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