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Title
Interactions between the local environmental factors within the female reproductive tract in physiological conditions and during Chlamydia trachomatis infection
Presenter
Elisabeth Menu
Authors
C. Adapen1, L. Réot1, C. Cannou2,1, N. Nunez3, R. Marlin1, J. Lemaître1, A.-S. Gallouet1, N. Bosquet1, L. de Chaisemartin4, O. Binois5, N. Achour Chneiweiss5, M.-T. Nugeyre2,1, R. Le Grand1, E. Menu2,1
Institutions
1Center for Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases, UMR 1184, Université Paris-Saclay, Inserm, CEA, IDMIT, Fontenay-aux-Roses, France, 2Institut Pasteur, Université Paris Cité, Mucosal Immunity and Sexually Transmitted Infection Control (MISTIC) Group, Virology, Paris, France, 3Life and Soft, Fontenay-aux-Roses, France, 4INSERM UMR 996, Inflammation, Chemokines and Immunopathology, Université Paris-Saclay, Châtenay-Malabry, France, 5Service de Biologie de la Reproduction, Préservation de la Fertilité, CECOS, Hôpital Antoine Béclère, Clamart, France

BACKGROUND: Heterosexual transmission from male to female is the major route of sexually transmitted infections (STI) and occurs mainly via the female reproductive tract (FRT) mucosae. Environmental factors present within the FRT play a role in the control against pathogens. An increase inflammation is rather in favour of a high risk of STI acquisition.
To have a better understanding of the interaction between the local environmental factors within the FRT in physiological conditions and during a STI, we have conducted three in vivo studies in the female cynomolgus macaque model.
METHODS: Firstly, we have studied the interplay between the vaginal microbiota and the local inflammation during the menstrual cycle. Secondly, the impact of vaginal microbiota manipulation on the inflammatory immune response and on Chlamydia trachomatis (CT) acquisition was analysed. Finally, semen being the main STI vector, we analysed the impact of seminal plasma (SP) and CT infection on the vaginal microbiota and inflammation. For all the studies, the menstrual cycle (progesterone measurement), cytokine production (blood and vaginal fluids) by LuminexÒ, neutrophil subpopulations (blood and vaginal cytobrushes) by flow cytometry and the vaginal microbiota (16S rRNA V3/V4 regions or full 16S) were analysed longitudinally.
RESULTS: We characterized for the first time the main cervicovaginal neutrophil subpopulations and demonstrated that local innate markers and vaginal microbiota composition are influenced by hormonal cycle phases. We highlighted an impact of the vaginal microbiota composition on the local and systemic immune responses induced by CT infection and a significant and persisting alteration of the vaginal microbiota upon antibiotics and CT infection/inoculation. We have shown that a single SP inoculation induced a higher inflammatory profile, with an increase production of cytokines and neutrophil extracellular traps (NET), compared to repeated SP inoculations. Furthermore, the immune responses to CT infection varied in the presence or absence of SP.
CONCLUSIONS: Our studies support the idea that strategies aiming at modulating the FRT inflammation could be effective to prevent adverse genital health outcomes such as STI acquisition. However, such strategies must remain efficient during semen exposition and during the entire menstrual cycle to have a significant effect on the genital health.

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