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 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.