Neonatal neutrophils stimulated by group B Streptococcus induce a proinflammatory T-helper cell bias.

Abstract

BackgroundGroup B Streptococcus (GBS) infection causes inflammatory co-morbidities in newborns. While the mechanisms remain unclear, evidence suggests that impaired innate-adaptive immune interactions may be contributory. We hypothesized that GBS-stimulated neonatal neutrophils provide a milieu that may drive pro-inflammatory T helper cell programming.MethodsNeutrophils were stimulated with Type III GBS (COH1); supernatants or intact neutrophils were co-cultured with CD4+ T cells or Treg cells. Resulting intracellular cytokines and nuclear transcription factors were determined by multicolor flow cytometry.ResultsGBS-stimulated neutrophils released soluble mediators that induced greater IL-17 responses in neonatal vs. adult CD4+ T cells in the absence of added polarizing cytokines. GBS-stimulated neonatal neutrophils also induced robust expression of the canonical nuclear transcription factors for Th1 (Tbet) and Th17 (IL-17) cells in CD4+ T cells. Following GBS stimulation, both intact neutrophils and neutrophil-derived mediators promoted the generation of Tregs with Th1 and Th17 characteristics.ConclusionGBS-stimulated neonatal neutrophils bias the in vitro Th differentiation program of neonatal CD4+ T cells and promote pro-inflammatory Th1 and Th17 phenotypes in Tregs. Our data suggest that developmental modifications of innate-adaptive immune cross-talk mechanisms may contribute to the inflammatory complications associated with neonatal GBS infection.