title: Reduced IL-17A Secretion Is Associated with High Levels of Pneumococcal Nasopharyngeal Carriage in Fijian Children.
abstract: Streptococcus pneumonia (the pneumococcus) is the leading vaccine preventable cause of serious infections in infants under 5 years of age. The major correlate of protection for pneumococcal infections is serotype-specific IgG antibody. More recently, antibody-independent mechanisms of protection have also been identified. Preclinical studies have found that IL-17 secreting CD4+ Th17 cells in reducing pneumococcal colonisation. This study assessed IL-17A levels in children from Fiji with high and low pneumococcal carriage density, as measured by quantitative real-time PCR (qPCR). We studied Th17 responses in 54 children who were designated as high density carriers (N=27, >8.21x10(5) CFU/ml) or low density carriers (N=27, <1.67x10(5) CFU/ml). Blood samples were collected, and isolated peripheral blood mononuclear cells (PBMCs) were stimulated for 6 days. Supernatants were harvested for cytokine analysis by multiplex bead array and/or ELISA. Th17 cytokines assayed included IL-17A, IL-21, IL-22 as well as TNF-α, IL-10, TGF-β, IL-6, IL-23 and IFNγ. Cytokine levels were significantly lower in children with high density pneumococcal carriage compared with children with low density carriage for IL-17A (p=0.002) and IL-23 (p=0.04). There was a trend towards significance for IL-22 (p=0.057) while no difference was observed for the other cytokines. These data provide further support for the role of Th17-mediated protection in humans and suggest that these cytokines may be important in the defence against pneumococcal carriage.
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Edwin
authors.initials: E
authors.lastname: Hoe
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Boelsen
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Zheng Quan
authors.initials: ZQ
authors.lastname: Toh
authors.affiliation: School of Applied Science, Republic Polytechnic, Singapore, Singapore.
authors.forename: Guang Wen
authors.initials: GW
authors.lastname: Sun
authors.affiliation: School of Applied Science, Republic Polytechnic, Singapore, Singapore.
authors.forename: Ghee Chong
authors.initials: GC
authors.lastname: Koo
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Balloch
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Marimla
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Dunne
authors.affiliation: Ministry of Health, Suva, Fiji.
authors.forename: Lisi
authors.initials: L
authors.lastname: Tikoduadua
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; Centre for International Child Health, Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Russell
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia; The Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Satzke
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: E Kim
authors.initials: EK
authors.lastname: Mulholland
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Licciardi
mesh_terms: D058491:Bacterial Load; D002648:Child; D002681:China; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood*; D008297:Male; D009305:Nasopharynx / Q000382:microbiology*; D013290:Streptococcal Infections / Q000097:blood* / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma