Dennis Nurjadi1,2, Marlon Kain3,2, Patrick Marcinek2, Marika Gaile2, Klaus Heeg1, Philipp Zanger1,3. 1. Institute for Medical Microbiology and Hygiene. 2. Institute of Tropical Medicine, University Hospitals, Eberhard Karls Universität, Tübingen, Germany. 3. Institute of Public Health, University Hospitals, Ruprecht-Karls-Universität, Heidelberg.
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.
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: Heather T Essigmann; Craig L Hanis; Stacia M DeSantis; William B Perkison; David A Aguilar; Goo Jun; D Ashley Robinson; Eric L Brown Journal: Microbiol Spectr Date: 2022-05-18
Authors: Lloyd S Miller; Vance G Fowler; Sanjay K Shukla; Warren E Rose; Richard A Proctor Journal: FEMS Microbiol Rev Date: 2020-01-01 Impact factor: 16.408