title: Ratio of T-Helper Type 1 (Th1) to Th17 Cytokines in Whole Blood Is Associated With Human β-Defensin 3 Expression in Skin and Persistent Staphylococcus aureus Nasal Carriage.
abstract: BACKGROUND
  Nasal colonization has gained attention as an effect modifier in Staphylococcus aureus vaccine trials, suggesting interference of carriage with T-cell immunity. Likewise, T-cell signals may be involved in regulating effectors of epithelial innate defense.
  
  
  METHODS
  Whole blood from 43 persistent carriers and 49 noncarriers was stimulated with viable S. aureus T-helper type 1 (Th1), Th2, and Th17 cytokine expression was measured, compared between carrier groups, and linked with data on human β-defensin 3 (hBD-3) messenger RNA (mRNA) in skin while adjusting for transcriptionally relevant promoter haplotypes.
  
  
  RESULTS
  Compared with carriers, stimulated whole blood from noncarriers contained on average 60% more interferon γ mRNA (P = .031) and 19% less interleukin 17A (IL-17A) mRNA (P = .11), resulting in, on average, a 90% higher IFN-γ to IL-17A mRNA ratio (P = .003). In a multivariable model, per duplication of the mRNA template, the risk of being a carrier increased by 93% for IL-17A (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.10-3.41; P = .023) and decreased by 35% for IFN-γ (OR, 0.65; 95% CI, 0.47-0.91; P = .01). Independent of carriage and DEFB promotor haplotype, a 1-unit increase in the IFN-γ to IL-17A mRNA ratio (mean ± SD, 5.93 ± 1.60) led to a 24% increase in hBD-3 transcription in experimentally wounded human skin (P = .003).
  
  
  CONCLUSIONS
  A low Th1 to Th17 mRNA ratio increases the propensity for persistent S. aureus nasal colonization, with downregulated hBD-3 transcription providing a potential link.
authors.affiliation: Institute for Medical Microbiology and Hygiene.|Institute of Tropical Medicine, University Hospitals, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Nurjadi
authors.affiliation: Institute of Public Health, University Hospitals, Ruprecht-Karls-Universität, Heidelberg.|Institute of Tropical Medicine, University Hospitals, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Marlon
authors.initials: M
authors.lastname: Kain
authors.affiliation: Institute of Tropical Medicine, University Hospitals, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcinek
authors.affiliation: Institute of Tropical Medicine, University Hospitals, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Marika
authors.initials: M
authors.lastname: Gaile
authors.affiliation: Institute for Medical Microbiology and Hygiene.
authors.forename: Klaus
authors.initials: K
authors.lastname: Heeg
authors.affiliation: Institute for Medical Microbiology and Hygiene.|Institute of Public Health, University Hospitals, Ruprecht-Karls-Universität, Heidelberg.
authors.forename: Philipp
authors.initials: P
authors.lastname: Zanger
mesh_terms: D000328:Adult; D002353:Carrier State / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D012867:Skin / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D023083:beta-Defensins / Q000032:analysis*
chemical_list: D016207:Cytokines; C422950:DEFB103A protein, human; D023083:beta-Defensins
keywords: T lymphocytes, helper-inducer; allergy and immunology; antimicrobial cationic peptides; colonization; commensalism; epidemiology; host-pathogen interactions; immunity, innate; immunoepidemiology; interferon γ; interleukin 10; interleukin 17