Polysaccharide capsule allows Group B Streptococcus to avoid killing in a newborn pneumonia model

Abstract

Abstract Group B Streptococcus (Streptococcus agalactiae, GBS) causes severe infections in neonates. While not a common adult pathogen, GBS is the leading cause of congenital pneumonia. To determine the molecular mechanisms of neonatal susceptibility, we developed a murine GBS pneumonia model. Neonatal, juvenile, and adult C57BL/6 mice were inoculated intranasally with 2800 CFU/g of GBS (COH1). After 7 d, survival was 100 % in adults and juveniles, with 10 % of neonates dying within 3 d after infection. Histopathological assessments showed severe lung injury scores 24 h after infection, with adult and juvenile mice demonstrating resolution of injury at 3 d post infection and normal histology after 7 d. In contrast, neonatal lungs had persistent lung injury up to 7 d post infection. By FACS, GBS induced rapid neutrophil recruitment into adult lungs and increased CD11b expression on adult lung macrophages. In neonatal lungs, GBS neither increased neutrophil numbers nor altered macrophage marker expression. Confocal imaging showed GBS in adult lungs almost entirely localized to alveolar macrophage phagolysosomes. However in neonatal lungs, GBS was only rarely phagocytosed by macrophages. These data were consistent with GBS killing data, which showed complete GBS killing within 24 h in adult and juvenile mice, but persistent GBS viability within the lung for up to 3 d in neonates. Defective GBS killing in neonates appeared to require the GBS capsule. Neonatal mice were much more efficient in killing the ΔcpsD capsule mutant compared to wild type GBS. Adult mice showed equal killing of ΔcpsD or wild type GBS. Our data suggest that the GBS capsule prevents killing by the newborn lung innate immune system, leading to neonatal disease susceptibility.