Microbiome, sex hormones, and immune responses in the reproductive tract: challenges for vaccine development against sexually transmitted infections

Abstract

The female and male reproductive tracts are complex eco-systems where immune cells, hormones, and microorganisms interact. The characteristics of the reproductive tract mucosa are distinct from other mucosal sites. Reproductive tract mucosal immune responses are compartmentalized, unique, and affected by resident bacterial communities and sex hormones. The female and male genital microbiomes are complex environments that fluctuate in response to external and host-associated stimuli. The female vaginal microbiota play an important role in preventing colonization by pathogenic organisms. Sex hormones and their duration of exposure affect the composition and stability of the microbiome as well as systemic and mucosal immune responses. In addition to the characteristics of the pathogen they are targeting, successful vaccines against sexually transmitted pathogens must take into account the differences between the systemic and mucosal immune responses, the compartmentalization of the mucosal immune responses, the unique characteristics of the reproductive tract mucosa, the role of the mucosal bacterial communities, the impact of sex hormones, and the interactions among all of these factors.

Keywords: Mucosal immunology; Review; Sex hormones; Sexually transmitted infections; Vaccines; Vaginal microbiota.

Figure 1

There are multiple potential interactions between the immune system, sex hormones, the microbiome and vaccine efficacy. Some of these interactions may be bidirectional. Vaccines against sexually transmitted pathogens should take into account all of these factors.

Figure 2

Heatmap showing the distribution of microbial taxa found in the vaginal microbial communities of 394 reproductive-age women. Adapted with permission from Proceedings of the National Academy of Sciences of the United States of America [52].

Figure 3

Percentage of vaginal bacterial community state types within each ethnic group of women. The number of women from each ethnic group is in parantheses. Reproduced with permission from Proceedings of the National Academy of Sciences of the United States of America [52].

Figure 4

Daily temporal dynamics of vaginal bacterial communities in six women over a 10-week period. The relative abudance of each phylotype is depicted as interpolated bar graphs. Phylotypes color codes are indicated on the right of each bar graph. Daily Nugent scores (range 0–10) and pH (range 4–7) are indicated below the graph. Red solid circles represent menstruation. Missing pH values are indicated by red box, otherwise pH is in line with a value of 4. Missing Nugent scores are also indicated by the red box, otherwise the score is in line with a score of 0. The figures show that the top four participants (A, B, C, D) carry highly stable communities dominated by L. crispatus (A), L. iners (B) and non-Lactobacillus dominated communities (C and D). Women E and F experienced very low stability communities with both high Nugent scores and pH. Unpublished data, personal communication from Ravel and Brotman.

Figure 5

Profiles of community state types, Nugent scores and menses for 32 women over a 16 week period. (A) Dendogram of distances between proportions of the five communities state types identified and measured within a woman over time. (B) Color bar indicates community class designation and is defined by clusters of proportions of community state types within a woman over time. (C) Profiles of community state types in which Nugent scores have been superimposed. Menses for each woman are indicated by boxes. Each time point is represented by a color-coded community state type (color key on top). Reproduced with permission from Science Translational Medicine.[54]