Sex hormones coordinate neutrophil immunity in the vagina by controlling chemokine gradients

Sandra Lasarte, Rafael Samaniego, Laura Salinas-Muñoz, Mauriel A. Guia-Gonzalez, Linnea A. Weiss, Enrique Mercader, Elena Ceballos-García, Teresa Navarro-González, Laura Moreno-Ochoa, Federico Perez-Millan, Marjorie Pion, Paloma Sanchez-Mateos, Andres Hidalgo, Maria A. Muñoz-Fernandez, Miguel Relloso

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Estradiol-based contraceptives and hormonal replacement therapy predispose women to Candida albicans infections. Moreover, during the ovulatory phase (high estradiol), neutrophil numbers decrease in the vaginal lumen and increase during the luteal phase (high progesterone). Vaginal secretions contain chemokines that drive neutrophil migration into the lumen. However, their expression during the ovarian cycle or in response to hormonal treatments are controversial and their role in vaginal defense remains unknown. To investigate the transepithelial migration of neutrophils, we used adoptive transfer of Cxcr2-/- neutrophils and chemokine immunofluorescence quantitative analysis in response to C. albicans vaginal infection in the presence of hormones. Our data show that the Cxcl1/Cxcr2 axis drives neutrophil transepithelial migration into the vagina. Progesterone promotes the Cxcl1 gradient to favor neutrophil migration. Estradiol disrupts the Cxcl1 gradient and favors neutrophil arrest in the vaginal stroma; as a result, the vagina becomes more vulnerable to pathogens.

Original languageEnglish
Pages (from-to)476-484
Number of pages9
JournalJournal of Infectious Diseases
Volume213
Issue number3
DOIs
StatePublished - 1 Feb 2016
Externally publishedYes

Keywords

  • C. albicans
  • Cxcl1
  • estradiol
  • neutrophils
  • progesterone

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