Background: Bacterial infections are a significant cause of adverse pregnancy outcomes. Ascending infection of lower genital tract bacteria such as Group B Streptococcus (GBS) lead to fetal injury, preterm births or stillbirths. Previous studies have indicated that the GBS hyaluronidase (HylB) enzyme degrades host hyaluronan into disaccharides, which dampen TLR2/4 signaling leading to increased systemic infections. Here, we aimed to understand how hyaluronan receptors contribute to ascending GBS infections.
Methods: Pregnant mice were vaginally inoculated at gestation day 13 or 14. Mice received 1x108 CFU of WT GBS strain GB37 (GB37 WT) or an isogenic hyaluronidase deficient strain (GB37DhylB) and were euthanized 72h post-challenge or at the onset of preterm labor. Intracellular cytokine staining and CFU counts were performed on pups and maternal tissue.
Results: HylB promotes ascending GBS infections in WT and CD44 deficient mice. Surprisingly, mice lacking TLR2/4 or IL-10 were able to curtail these infections. Notably, IL-10+ macrophages were significantly increased in the uterine tissues of WT mice compared to TLR2/4 deficient mice that were infected with HylB proficient GBS, which likely promotes immune suppression and GBS dissemination.
Conclusion: Collectively, these observations suggest that GBS HylB promotes immune suppression via inhibition of TLR2/4 and the promotion of IL-10. This results in a local anti-inflammatory environment in the pregnant uterus, as evidenced by the presence of IL-10-expressing uterine macrophages.