Severely depressed interleukin-17 production by human neonatal mononuclear cells.

ABSTRACT

BACKGROUND: The role of T-helper 17 cells (Th17) in neonatal host defense remains to be fully elucidated. Interleukin (IL)-17 plays an important role in the immune response to bacterial and fungal pathogens by promoting inflammation. METHODS: We examined neonatal production of IL-17 in mixed mononuclear cells (MMCs) isolated from umbilical cord blood for comparison with adult peripheral blood mononuclear cell controls. RESULTS: IL-17 production was profoundly diminished in MMCs isolated from cord blood when compared with MMCs from adult blood. This was associated with a marked reduction in the population of CCR6+ IL-17(+) T-cells in the neonatal cord blood. We also found diminished intracellular formation of IL-17, and diminished IL-17 responses to both group B streptococci (GBS) and Escherichia coli. Neonatal mononuclear cells were found to adequately phosphorylate signal transducer and activator of transcription 3, pY705, and pS727. We and others have reported markedly reduced interferon-γ production by neonate mononuclear cells exposed to GBS. Here, we correct that profound abnormality with added IL-17. CONCLUSION: Our results suggest that profound deficiency of IL-17 production associated with a marked decrease in Th17 cells likely contributes significantly to the increased susceptibility of human neonates to invasive bacterial and fungal infections.