Role of the human vaginal microbiota in the regulation of inflammation and sexually transmitted infection acquisition: Contribution of the non-human primate model to a better understanding?

Abstract

The human vaginal microbiota has a central role in the regulation of the female reproductive tract (FRT) inflammation. Indeed, on one hand an optimal environment leading to a protection against sexually transmitted infections (STI) is associated with a high proportion of Lactobacillus spp. (eubiosis). On the other hand, a more diverse microbiota with a high amount of non-Lactobacillus spp. (dysbiosis) is linked to a higher local inflammation and an increased STI susceptibility. The composition of the vaginal microbiota is influenced by numerous factors that may lead to a dysbiotic environment. In this review, we first discuss how the vaginal microbiota composition affects the local inflammation with a focus on the cytokine profiles, the immune cell recruitment/phenotype and a large part devoted on the interactions between the vaginal microbiota and the neutrophils. Secondly, we analyze the interplay between STI and the vaginal microbiota and describe several mechanisms of action of the vaginal microbiota. Finally, the input of the NHP model in research focusing on the FRT health including vaginal microbiota or STI acquisition/control and treatment is discussed.

Keywords: cytokines; inflammation; neutrophils; non-human primates; sexually transmitted infections; vaginal microbiota.

Figure 1

Vaginal microbiota and female reproductive tract inflammation. An eubiotic vaginal microbiota is dominated by Lactobacillus spp. that can produce different metabolites such as sugar, lactate, amino acid and dipeptide. This environment is associated with a low inflammation including cytokine production and immune cells recruitment (left panel). On the contrary, a more diverse vaginal microbiota (low Lactobacillus spp. and high anaerobic bacteria abundances) is associated with an increased inflammation. The microbial environment leads to the production of metabolites linked to vaginal discomfort such as vaginal discharges or amine odor. In this context, higher production of cytokines and recruitment of T cells (Th17 and CCR5+ CD4+ T cells) are detected (right panel). Created with BioRender.com.

Figure 2

Association between factors affecting the vaginal microbiota and the effect on inflammation. The vaginal microbiota can be influenced by numerous factors including sexually transmitted infection, hormonal contraception, menstrual cycle, ethnicity, sexual behaviors, hygiene practices, stress, nutrition etc. Those factors by influencing the vaginal microbiota will affect the FRT inflammation including cytokine production, T cell recruitment and neutrophil activation and maturation. Created with BioRender.com.

Figure 3

Mechanisms of action associated with Lactobacillus spp. presence. Lactobacillus spp. decrease the risk of sexually transmitted infection acquisition by several mechanisms: (1) Aggregation to epithelial cells protecting the cells from pathogen; (2) Maintenance of mucus integrity; (3) Low inflammation (low production of cytokine and immune cells recruitment); (4) Production of factors (lactic acid, bacteriocins, H₂O₂, extracellular vesicles) involved in pathogen inhibition. Created with BioRender.com.

Figure 4

Contribution of the female NHP model in the understanding of the mechanisms involved in sexually transmitted infection acquisition and control. NHP and Human similarities include NHP susceptibility to several STI affecting Human, FRT anatomy, menstrual cycle, immune cells presence and vaginal microbiota composition. This model also allows the longitudinal collection of tissue samples, stool, blood or cervicovaginal fluids. Therefore, NHP can be used to study various parameters involved in STI acquisition and control including time and route of infection, susceptibility to infection/co-infection, physiopathology, hormone effects, in deep evaluation of the immune system, probiotic/prebiotic/vaccine/drug testing. Created with BioRender.com.