title: Reduced T-Helper 17 Responses to Streptococcus pneumoniae in Infection-Prone Children Can Be Rescued by Addition of Innate Cytokines.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Reduced Th17 responses to S. pneumoniae in PBMCs of IP children can be rescued by addition of Th17-promoting cytokines.
authors.affiliation: Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute and.
authors.forename: Saleem
authors.initials: S
authors.lastname: Basha
authors.affiliation: Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute and.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Kaur
authors.affiliation: Human Immunology Center, University of Rochester Medical Center, New York.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Mosmann
authors.affiliation: Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute and.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pichichero
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology*; D011446:Prospective Studies; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D016207:Cytokines; D014157:Transcription Factors
keywords: Pneumococcus; Th17; innate cytokines; young children.