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

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 beta-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 gamma mRNA (P = .031) and 19% less interleukin 17A (IL-17A) mRNA (P = .11), resulting in, on average, a 90% higher IFN-gamma 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-gamma (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-gamma 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 down-regulated hBD-3 transcription providing a potential link.