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

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, 1ß, and 23 and transforming growth factor ß) 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.