Reduced T-Helper 17 Responses to Streptococcus pneumoniae in Infection-Prone Children Can Be Rescued by Addition of Innate Cytokines

J Infect Dis. 2017 Apr 15;215(8):1321-1330. doi: 10.1093/infdis/jix090.

Abstract

Background: T-helper (Th) 17 cells are important in the control of Streptococcus pneumoniae. We sought to understand the mechanism of failure of Th17 immunity resulting in S. pneumoniae infections in children <2 years old.

Methods: Peripheral blood mononuclear cells (PBMCs) from infection-prone (IP) and non-IP (NIP) children 9-18 months old were examined for their responses to heat-killed S. Pneumoniae, using flow cytometry, reverse-transcription polymerase chain reaction, and enzyme-linked immunoassay. We measured cytokine production, proliferation, and differentiation of Th17 cells and the expression of transcription factors in response to S. pneumoniae.

Results: PBMCs of IP children stimulated with heat-killed S. pneumoniae had significantly reduced percentages of CD4+ Th1 (interleukin2, tumor necrosis factor α) and Th17 (interleukin 17A) cells compared with NIP children. Addition of exogenous Th17-promoting cytokines (interleukin 6, 1β, and 23 and transforming growth factor β) restored CD4+ Th17 cell function in cells from IP children to levels measured in NIP children.

Conclusions: Reduced Th17 responses to S. pneumoniae in PBMCs of IP children can be rescued by addition of Th17-promoting cytokines.

Keywords: Pneumococcus; Th17; innate cytokines; young children..

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunity, Innate
  • Infant
  • Leukocytes, Mononuclear / immunology
  • Longitudinal Studies
  • Male
  • Otitis Media / immunology
  • Otitis Media / microbiology
  • Pneumococcal Infections / immunology*
  • Prospective Studies
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Transcription Factors / metabolism

Substances

  • Cytokines
  • Transcription Factors