Exopolysaccharides of Lactobacillus crispatus mediate key balancing interactions with the vaginal mucosa
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (Arcadia Science)
Abstract
Lactobacillus crispatus is a dominant member of the healthy vaginal microbiota, yet the mechanisms by which it modulates host immunity remain poorly defined, in part due to the lack of tractable in vivo models. Here, we integrate bacterial genetics, in vitro epithelial systems, human-derived data and proteomic approach (Olink) to uncover a critical role for L. crispatus exopolysaccharides (EPS) in shaping the bacteria-vagina interactions. Comparative genomics identified a conserved EPS biosynthetic locus, with the priming glycosyltransferase gene epsE emerging as a regulatory node, in line with its distinct expression in human vaginal samples. Functional disruption of epsE abrogated L. crispatus EPS production and revealed its role for immune modulation. In human vaginal epithelial monolayers, EPS presence enhanced immune-regulatory (LAP TGF-beta-1) and anti-inflammatory (CST5) responses, whereas its absence triggered elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-8) and matrix metalloproteinase (MMP-10). In a 3D vaginal organotypic model, EPS increased chemokines (CXCL5, CXCL6) linked to immune surveillance and the presence of the markers was validated in vaginal samples of healthy volunteers. These findings position EPS as a key immunomodulatory structure of L. crispatus , advancing our mechanistic understanding of host-commensal interactions and informing microbiome-based strategies to promote vaginal health.
Article activity feed
-
Very interesting work to reveal immunomodulatory mechanisms of Lactobacillus species in the vaginal microbiome.
The background on the loss of espBCD genes in many Lactobacillus species and retention of espA in host-associated taxa is very interesting. It would be good to reference Figure 1 after lines 116-118.
In the future, it would help the reader to label each figure as they appear within the text to make it easier when cross referencing the figure legends at the end.
In Figure 2, the TEM micrographs comparing the seem show that WT have more EPS, but the dark cloud around the EPS mutant makes it hard to tell if it's more EPS or none. The methods say that three micrographs were analyzed, but panel B shows n=2. It would be good to clarify the number of cells per image and if it was quantified by area of the dark cloud around the cell.
T…
Very interesting work to reveal immunomodulatory mechanisms of Lactobacillus species in the vaginal microbiome.
The background on the loss of espBCD genes in many Lactobacillus species and retention of espA in host-associated taxa is very interesting. It would be good to reference Figure 1 after lines 116-118.
In the future, it would help the reader to label each figure as they appear within the text to make it easier when cross referencing the figure legends at the end.
In Figure 2, the TEM micrographs comparing the seem show that WT have more EPS, but the dark cloud around the EPS mutant makes it hard to tell if it's more EPS or none. The methods say that three micrographs were analyzed, but panel B shows n=2. It would be good to clarify the number of cells per image and if it was quantified by area of the dark cloud around the cell.
The use of confocal microscopy and SEM really shows how the bacteria interact with the monolayer of cells (Figure 5). Did you consider using spent media from WT and EPS mutant cells as a negative control. What was measured from these images? The cell layer in c and f certainly appear different, but the bacteria seem to be more abundant than in b and e with the WT strain.
-
