Local innate markers and vaginal microbiota composition are influenced by hormonal cycle phases

Autor: Adapen, Cindy, Réot, Louis, Nunez, Natalia, Cannou, Claude, Marlin, Romain, Lemaître, Julien, d'Agata, Léo, Gilson, Emmanuel, Ginoux, Eric, Le Grand, Roger, Nugeyre, Marie-Thérèse, Menu, Elisabeth
Přispěvatelé: Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Life & Soft [Fontenay-aux-Roses], Mucosal Immunity and Sexually Transmitted Infection Control (MISTIC), Institut Pasteur [Paris] (IP), The program was funded by the Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure supported by the 'Programme Investissements d’Avenir', managed by the ANR under reference ANR-11-INBS-0008, as well as Sidaction 'financement jeune chercheur' under reference '2019-2-FJC-1234'. The Non-Human Primate study is part of the TracVac project, which received financial support from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 733373., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), European Project: 733373,TracVac, MENU, Elisabeth, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, Developing a Chlamydia Trachomatis vaccine - SOCIETAL CHALLENGES - Health, demographic change and well-being - TracVac - - 733373 - INCOMING
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Immunology
Frontiers in Immunology, 2022, 13, pp.841723. ⟨10.3389/fimmu.2022.841723⟩
ISSN: 1664-3224
DOI: 10.3389/fimmu.2022.841723⟩
Popis: 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.
Databáze: OpenAIRE