title: Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-γ and IgG3 Responses Compared with Children.
abstract: Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first detailed characterization of the human adaptive immune response against S. pyogenes in both children and adults. We report that all adults in our study, as well as most children, showed immunity against the two conserved group A streptococci (GAS) Ags, streptococcal C5a peptidase and immunogenic secreted protein. The response primarily consisted of three subsets of Th1 T cells, in which the TNF-α(+) and IL-2(+)TNF-α(+) subsets were most frequent. Humoral immunity was dominated by IgG1 and IgG3, whereas the Th2-associated IgG4 isotype was only detected at very low amounts. IgG3 levels correlated significantly with IFN-γ, but not with IL-5, IL-13, IL-17, or TNF-α. Interestingly, children showed a similar pattern of Ag-specific cytokine release, but displayed significantly lower levels of IgG3 and IFN-γ compared with adults. Thus, human immune responses against S. pyogenes consist of a robust Th1 cellular memory response in combination with IgG1/IgG3-dominated humoral immunity that increase with age. The significance of these data regarding both the increased GAS infection rate in children and the development of protective GAS vaccines is discussed.
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, DK-2300 Copenhagen S, Denmark; Department of Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark; and jdi@ssi.dk rjm@ssi.dk.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Mortensen
authors.affiliation: Department of Pediatrics, Copenhagen University Hospital, Hvidovre, DK-2650 Hvidovre, Denmark.
authors.forename: Thomas Nørrelykke
authors.initials: TN
authors.lastname: Nissen
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, DK-2300 Copenhagen S, Denmark;
authors.forename: Thomas
authors.initials: T
authors.lastname: Blauenfeldt
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark; and.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Christensen
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, DK-2300 Copenhagen S, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, DK-2300 Copenhagen S, Denmark; jdi@ssi.dk rjm@ssi.dk.
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D013290:Streptococcal Infections / Q000276:immunology* / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G; D007371:Interferon-gamma