title: Characterization of Th17 responses to Streptococcus pneumoniae in humans: comparisons between adults and children in a developed and a developing country.
abstract: Intranasal exposure to Streptococcus pneumoniae as well as mucosal or parenteral immunization with a recently developed killed pneumococcal whole cell vaccine, confer Th17-mediated protection against subsequent S. pneumoniae colonization in mice. Given our interest in the function of Th17 cells and the ongoing efforts to develop this vaccine for use in infants and children in developing countries, we analyzed Th17 responses to the whole cell antigen (WCA) and individual pneumococcal antigens in healthy individuals and patients with pneumococcal disease and compared responses in children and adults from Sweden and Bangladesh. Peripheral blood mononuclear cells (PBMCs) isolated from Swedish adults produced IL-17A after stimulation with WCA, with the pneumolysoid PdT and with the protein required for cell separation in group B streptococci (PcsB). IL-22 and IFN-γ responses were also detected, but these cytokines originated from separate CD4+ T cell subsets. PBMCs from Swedish children produced lower levels of IL-17A in response to WCA compared to adults, whereas no such difference was noted from the samples from Bangladesh, where responses by children and adults were both significantly higher than those in Sweden. High IL-17A responses to stimulation with WCA were also observed in children with proven or probable pneumococcal pneumonia. Our results thus demonstrate the presence of Th17-type T cells that are specific for pneumococcus in both children and adults. The different levels of Th17 responses to pneumococci in children and adults in developing and developed countries, which may at least partly be due to differences in exposure to pneumococci, are important factors to consider in the evaluation of candidate pneumococcal protein-based vaccines in human trials.
authors.affiliation: Gothenburg University Vaccine Research Institute (GUVAX), Department of Microbiology and Immunology, University of Gothenburg, Box 435, 405 30, Gothenburg, Sweden. anna.lundgren@microbio.gu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Lundgren
authors.forename: Taufiqur R
authors.initials: TR
authors.lastname: Bhuiyan
authors.forename: Daniel
authors.initials: D
authors.lastname: Novak
authors.forename: Joanna
authors.initials: J
authors.lastname: Kaim
authors.forename: Adi
authors.initials: A
authors.lastname: Reske
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.forename: Richard
authors.initials: R
authors.lastname: Malley
mesh_terms: D000328:Adult; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001459:Bangladesh; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D019049:Developed Countries; D003906:Developing Countries; D005260:Female; D006801:Humans; D007223:Infant; D020381:Interleukin-17 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013548:Sweden; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; C508717:IL17A protein, human; D020381:Interleukin-17; D022242:Pneumococcal Vaccines