Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases
BackgroundThe female reproductive tract (FRT) mucosa is the first line of defense against sexually transmitted infection (STI). FRT environmental factors, including immune-cell composition and the vaginal microbiota, interact with each other to modulate susceptibility to STIs. Moreover, the menstrua...
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| Format: | Article |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.841723/full |
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| author | Cindy Adapen Louis Réot Natalia Nunez Claude Cannou Claude Cannou Romain Marlin Julien Lemaître Léo d’Agata Emmanuel Gilson Eric Ginoux Roger Le Grand Marie-Thérèse Nugeyre Marie-Thérèse Nugeyre Elisabeth Menu Elisabeth Menu |
| author_facet | Cindy Adapen Louis Réot Natalia Nunez Claude Cannou Claude Cannou Romain Marlin Julien Lemaître Léo d’Agata Emmanuel Gilson Eric Ginoux Roger Le Grand Marie-Thérèse Nugeyre Marie-Thérèse Nugeyre Elisabeth Menu Elisabeth Menu |
| author_sort | Cindy Adapen |
| collection | DOAJ |
| description | BackgroundThe female reproductive tract (FRT) mucosa is the first line of defense against sexually transmitted infection (STI). FRT environmental factors, including immune-cell composition and the vaginal microbiota, interact with each other to modulate susceptibility to STIs. Moreover, the menstrual cycle induces important modifications within the FRT mucosa. Cynomolgus macaques are used as a model for the pathogenesis and prophylaxis of STIs. In addition, their menstrual cycle and FRT morphology are similar to women. The cynomolgus macaque vaginal microbiota is highly diverse and similar to dysbiotic vaginal microbiota observed in women. However, the impact of the menstrual cycle on immune markers and the vaginal microbiota in female cynomolgus macaques is unknown. We conducted a longitudinal study covering three menstrual cycles in cynomolgus macaques. The evolution of the composition of the vaginal microbiota and inflammation (cytokine/chemokine profile and neutrophil phenotype) in the FRT and blood was determined throughout the menstrual cycle.ResultsCervicovaginal cytokine/chemokine concentrations were affected by the menstrual cycle, with a peak of production during menstruation. We observed three main cervicovaginal neutrophil subpopulations: CD11bhigh CD101+ CD10+ CD32a+, CD11bhigh CD101+ CD10- CD32a+, and CD11blow CD101low CD10- CD32a-, of which the proportion varied during the menstrual cycle. During menstruation, there was an increase in the CD11bhigh CD101+ CD10+ CD32a+ subset of neutrophils, which expressed higher levels of CD62L. Various bacterial taxa in the vaginal microbiota showed differential abundance depending on the phase of the menstrual cycle. Compilation of the factors that vary according to hormonal phase showed the clustering of samples collected during menstruation, characterized by a high concentration of cytokines and an elevated abundance of the CD11bhigh CD101+ CD10+ CD32a+ CD62L+ neutrophil subpopulation.ConclusionsWe show a significant impact of menstruation on the local environment (cytokine production, neutrophil phenotype, and vaginal microbiota composition) in female cynomolgus macaques. Menstruation triggers increased production of cytokines, shift of the vaginal microbiota composition and the recruitment of mature/activated neutrophils from the blood to the FRT. These results support the need to monitor the menstrual cycle and a longitudinal sampling schedule for further studies in female animals and/or women focusing on the mucosal FRT environment. |
| first_indexed | 2024-04-13T16:37:03Z |
| format | Article |
| id | doaj.art-369f4a48cda9426a82d646994eb65b87 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T16:37:03Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-369f4a48cda9426a82d646994eb65b872022-12-22T02:39:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.841723841723Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle PhasesCindy Adapen0Louis Réot1Natalia Nunez2Claude Cannou3Claude Cannou4Romain Marlin5Julien Lemaître6Léo d’Agata7Emmanuel Gilson8Eric Ginoux9Roger Le Grand10Marie-Thérèse Nugeyre11Marie-Thérèse Nugeyre12Elisabeth Menu13Elisabeth Menu14Université Paris-Saclay, Inserm, Commissariat à l'énergie Atomique et aux énergies Alternatives (CEA), Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases [IMVA-HB/Infectious Disease Models and Innovative Therapies (IDMIT)], Fontenay-aux-Roses, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'énergie Atomique et aux énergies Alternatives (CEA), Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases [IMVA-HB/Infectious Disease Models and Innovative Therapies (IDMIT)], Fontenay-aux-Roses, FranceLife&Soft, Fontenay-aux-Roses, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'énergie Atomique et aux énergies Alternatives (CEA), Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases [IMVA-HB/Infectious Disease Models and Innovative Therapies (IDMIT)], Fontenay-aux-Roses, FranceMucosal Immunity and Sexually Transmitted Infection Control (MISTIC) Group, Department of Virology, Institut Pasteur, Paris, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'énergie Atomique et aux énergies Alternatives (CEA), Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases [IMVA-HB/Infectious Disease Models and Innovative Therapies (IDMIT)], Fontenay-aux-Roses, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'énergie Atomique et aux énergies Alternatives (CEA), Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases [IMVA-HB/Infectious Disease Models and Innovative Therapies (IDMIT)], Fontenay-aux-Roses, FranceLife&Soft, Fontenay-aux-Roses, FranceLife&Soft, Fontenay-aux-Roses, FranceLife&Soft, Fontenay-aux-Roses, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'énergie Atomique et aux énergies Alternatives (CEA), Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases [IMVA-HB/Infectious Disease Models and Innovative Therapies (IDMIT)], Fontenay-aux-Roses, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'énergie Atomique et aux énergies Alternatives (CEA), Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases [IMVA-HB/Infectious Disease Models and Innovative Therapies (IDMIT)], Fontenay-aux-Roses, FranceMucosal Immunity and Sexually Transmitted Infection Control (MISTIC) Group, Department of Virology, Institut Pasteur, Paris, FranceUniversité Paris-Saclay, Inserm, Commissariat à l'énergie Atomique et aux énergies Alternatives (CEA), Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases [IMVA-HB/Infectious Disease Models and Innovative Therapies (IDMIT)], Fontenay-aux-Roses, FranceMucosal Immunity and Sexually Transmitted Infection Control (MISTIC) Group, Department of Virology, Institut Pasteur, Paris, FranceBackgroundThe female reproductive tract (FRT) mucosa is the first line of defense against sexually transmitted infection (STI). FRT environmental factors, including immune-cell composition and the vaginal microbiota, interact with each other to modulate susceptibility to STIs. Moreover, the menstrual cycle induces important modifications within the FRT mucosa. Cynomolgus macaques are used as a model for the pathogenesis and prophylaxis of STIs. In addition, their menstrual cycle and FRT morphology are similar to women. The cynomolgus macaque vaginal microbiota is highly diverse and similar to dysbiotic vaginal microbiota observed in women. However, the impact of the menstrual cycle on immune markers and the vaginal microbiota in female cynomolgus macaques is unknown. We conducted a longitudinal study covering three menstrual cycles in cynomolgus macaques. The evolution of the composition of the vaginal microbiota and inflammation (cytokine/chemokine profile and neutrophil phenotype) in the FRT and blood was determined throughout the menstrual cycle.ResultsCervicovaginal cytokine/chemokine concentrations were affected by the menstrual cycle, with a peak of production during menstruation. We observed three main cervicovaginal neutrophil subpopulations: CD11bhigh CD101+ CD10+ CD32a+, CD11bhigh CD101+ CD10- CD32a+, and CD11blow CD101low CD10- CD32a-, of which the proportion varied during the menstrual cycle. During menstruation, there was an increase in the CD11bhigh CD101+ CD10+ CD32a+ subset of neutrophils, which expressed higher levels of CD62L. Various bacterial taxa in the vaginal microbiota showed differential abundance depending on the phase of the menstrual cycle. Compilation of the factors that vary according to hormonal phase showed the clustering of samples collected during menstruation, characterized by a high concentration of cytokines and an elevated abundance of the CD11bhigh CD101+ CD10+ CD32a+ CD62L+ neutrophil subpopulation.ConclusionsWe show a significant impact of menstruation on the local environment (cytokine production, neutrophil phenotype, and vaginal microbiota composition) in female cynomolgus macaques. Menstruation triggers increased production of cytokines, shift of the vaginal microbiota composition and the recruitment of mature/activated neutrophils from the blood to the FRT. These results support the need to monitor the menstrual cycle and a longitudinal sampling schedule for further studies in female animals and/or women focusing on the mucosal FRT environment.https://www.frontiersin.org/articles/10.3389/fimmu.2022.841723/fullinflammationmenstrual cyclefemale reproductive tract (FRT)cytokinesblood compartmentneutrophils |
| spellingShingle | Cindy Adapen Louis Réot Natalia Nunez Claude Cannou Claude Cannou Romain Marlin Julien Lemaître Léo d’Agata Emmanuel Gilson Eric Ginoux Roger Le Grand Marie-Thérèse Nugeyre Marie-Thérèse Nugeyre Elisabeth Menu Elisabeth Menu Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases Frontiers in Immunology inflammation menstrual cycle female reproductive tract (FRT) cytokines blood compartment neutrophils |
| title | Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases |
| title_full | Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases |
| title_fullStr | Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases |
| title_full_unstemmed | Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases |
| title_short | Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases |
| title_sort | local innate markers and vaginal microbiota composition are influenced by hormonal cycle phases |
| topic | inflammation menstrual cycle female reproductive tract (FRT) cytokines blood compartment neutrophils |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.841723/full |
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