title: Sex Hormones Coordinate Neutrophil Immunity in the Vagina by Controlling Chemokine Gradients.
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.
authors.affiliation: Laboratorio InmunoBiología Molecular, Grupo Fisiopatología Comparada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lasarte
authors.affiliation: Unidad de Microscopía Confocal, Hospital General Universitario Gregorio Marañón (HGUGM) and Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM).
authors.forename: Rafael
authors.initials: R
authors.lastname: Samaniego
authors.affiliation: Laboratorio InmunoBiología Molecular, Grupo Fisiopatología Comparada.
authors.forename: Laura
authors.initials: L
authors.lastname: Salinas-Muñoz
authors.affiliation: Laboratorio InmunoBiología Molecular, Grupo Fisiopatología Comparada.
authors.forename: Mauriel A
authors.initials: MA
authors.lastname: Guia-Gonzalez
authors.affiliation: Area of Cell and Developmental Biology, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC).
authors.forename: Linnea A
authors.initials: LA
authors.lastname: Weiss
authors.affiliation: Laboratorio InmunoBiología Molecular, Grupo Fisiopatología Comparada.
authors.forename: Enrique
authors.initials: E
authors.lastname: Mercader
authors.affiliation: Laboratorio InmunoBiología Molecular, Grupo Fisiopatología Comparada Servicio de Ginecología.
authors.forename: Elena
authors.initials: E
authors.lastname: Ceballos-García
authors.affiliation: Servicio de Ginecología.
authors.forename: Teresa
authors.initials: T
authors.lastname: Navarro-González
authors.affiliation: Servicio de Ginecología.
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno-Ochoa
authors.affiliation: Servicio de Ginecología.
authors.forename: Federico
authors.initials: F
authors.lastname: Perez-Millan
authors.affiliation: Laboratorio InmunoBiología Molecular.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Pion
authors.affiliation: Laboratorio de Inmuno-oncología, Hospital General Universitario Gregorio Marañón (HGUGM) and Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid.
authors.forename: Paloma
authors.initials: P
authors.lastname: Sanchez-Mateos
authors.affiliation: Area of Cell and Developmental Biology, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC).
authors.forename: Andres
authors.initials: A
authors.lastname: Hidalgo
authors.affiliation: Laboratorio InmunoBiología Molecular Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Muñoz-Fernandez
authors.affiliation: Laboratorio InmunoBiología Molecular, Grupo Fisiopatología Comparada.
authors.forename: Miguel
authors.initials: M
authors.lastname: Relloso
mesh_terms: D000328:Adult; D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D014621:Vagina / Q000166:cytology* / Q000276:immunology
chemical_list: D018925:Chemokines; D004967:Estrogens; D023063:Receptors, Interleukin-8B; D011374:Progesterone
keywords: C. albicans; Cxcl1; estradiol; neutrophils; progesterone