Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females

Olivia J. Hall, Nathachit Limjunyawong, Meghan S. Vermillion, Dionne P. Robinson, Nicholas Wohlgemuth, Andrew Pekosz, Wayne A Mitzner, Sabra L Klein

Research output: Contribution to journalArticle

Abstract

Over 100 million women use progesterone therapies worldwide. Despite having immunomodulatory and repair properties, their effects on the outcome of viral diseases outside of the reproductive tract have not been evaluated. Administration of exogenous progesterone (at concentrations that mimic the luteal phase) to progesterone-depleted adult female mice conferred protection from both lethal and sublethal influenza A virus (IAV) infection. Progesterone treatment altered the inflammatory environment of the lungs, but had no effects on viral load. Progesterone treatment promoted faster recovery by increasing TGF-β, IL-6, IL-22, numbers of regulatory Th17 cells expressing CD39, and cellular proliferation, reducing protein leakage into the airway, improving pulmonary function, and upregulating the epidermal growth factor amphiregulin (AREG) in the lungs. Administration of rAREG to progesterone-depleted females promoted pulmonary repair and improved the outcome of IAV infection. Progesterone-treatment of AREG-deficient females could not restore protection, indicating that progesterone-mediated induction of AREG caused repair in the lungs and accelerated recovery from IAV infection. Repair and production of AREG by damaged respiratory epithelial cell cultures in vitro was increased by progesterone. Our results illustrate that progesterone is a critical host factor mediating production of AREG by epithelial cells and pulmonary tissue repair following infection, which has important implications for women’s health.

Original languageEnglish (US)
Article numbere1005840
JournalPLoS Pathogens
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2016

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Human Influenza
Progesterone
Lung
Virus Diseases
Influenza A virus
Therapeutics
Epithelial Cells
Th17 Cells
Luteal Phase
Women's Health
Viral Load
Epidermal Growth Factor
Interleukin-6
Cell Culture Techniques
Cell Proliferation
Amphiregulin
Infection

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females. / Hall, Olivia J.; Limjunyawong, Nathachit; Vermillion, Meghan S.; Robinson, Dionne P.; Wohlgemuth, Nicholas; Pekosz, Andrew; Mitzner, Wayne A; Klein, Sabra L.

In: PLoS Pathogens, Vol. 12, No. 9, e1005840, 01.09.2016.

Research output: Contribution to journalArticle

Hall, Olivia J. ; Limjunyawong, Nathachit ; Vermillion, Meghan S. ; Robinson, Dionne P. ; Wohlgemuth, Nicholas ; Pekosz, Andrew ; Mitzner, Wayne A ; Klein, Sabra L. / Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females. In: PLoS Pathogens. 2016 ; Vol. 12, No. 9.
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