Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor

Abstract

Group B streptococci overcome neutrophils in placental membranes, inducing fetal injury and preterm labor.

Hyaluronidase Impairs Neutrophil Function and Promotes Group BStreptococcusInvasion and Preterm Labor in Nonhuman Primates

“…Despite the significant adverse outcomes noted in the GB37-infected group, there was no statistical difference in the peak AF cytokine levels among the three treatment groups of this study (i.e., saline, GB37, and GB37Δ hylB ; Table 1 ). Interestingly, compared to our previously published studies on hyperhemolytic GBSΔ covR -inoculated animals ( 28 ), where we reported peak AF interleukin-6 (IL-6) and IL-8 ranging between 15 and 22 ng/ml (for animals with microbial invasion of the amniotic cavity), the GB37 group had significantly lower peak AF levels of IL-6 ( P = 0.009) and IL-8 ( P = 0.02). Taken together, these results suggest that increased AF cytokines such as IL-6 and IL-8 are not necessarily a predictive signature of preterm labor, particularly during infection with the immunosuppressive hyaluronidase-expressing GBS bacteria.…”

“…To elucidate whether hyaluronidase promotes GBS infection and adverse outcomes during pregnancy, we used a chronically catheterized nonhuman primate ( Macaca nemestrina ) model that closely emulates human pregnancy and defines temporal events during amniotic cavity invasion and preterm labor ( 28 ). Ten animals received choriodecidual inoculations of 1 × 10 8 to 3 × 10 8 CFU of either hyaluronidase-proficient wild-type GBS (strain GB37, n = 5) or an isogenic hyaluronidase-deficient GBS (strain GB37Δ hylB , n = 5).…”

“…Adverse pregnancy outcomes, specifically preterm labor and/or microbial invasion of the amniotic cavity ( Table 1 ) were the primary outcomes of our study. In GBS-inoculated animals, Cesarean section was performed at the onset of preterm labor, which was defined as progressive cervical dilation associated with increased and sustained uterine activity or at 3 days post-GBS inoculation if preterm labor did not occur, as described previously ( 28 ).…”

“…P values between 0.05 and 0.1 are noted due to the small sample size of this nonhuman primate study but were not considered significant. Since fetal tissue lysates were not available from historical saline animals ( n = 4) reported previously ( 28 ), only saline animals performed in the present study ( n = 2) were included in these analyses.…”

“…Similarities of NHPs to humans include reproductive anatomy, type and structure of placenta (hemomonochorial), number of fetuses (singleton), long gestational period (160 to 170 days), initiation of labor (hormonal control of parturition), sensitivity to pathogens, and the developmental timeline of the fetal lung and brain ( 25 , 26 ). In the chronically catheterized pregnant NHP model ( 27 , 28 ), we inoculate bacteria at the choriodecidual space, a site in the pregnant uterine mucosa between the uterine muscle and the placental membranes, where bacteria are thought to first encounter the maternal-fetal interface during ascending infection from the lower genital tract ( 2 , 27 ).…”