D Nurjadi1, K Heeg2, A N R Weber3, P Zanger4. 1. Department of Infectious Diseases, Medical Microbiology and Hygiene, University Hospitals, Heidelberg, Germany; Institute of Tropical Medicine, University Hospitals, Tübingen, Germany. 2. Department of Infectious Diseases, Medical Microbiology and Hygiene, University Hospitals, Heidelberg, Germany. 3. Department of Immunology, Interfaculty Institute for Cell Biology, Eberhard-Karls-Universität, Tübingen, Germany. 4. Department of Infectious Diseases, Medical Microbiology and Hygiene, University Hospitals, Heidelberg, Germany; Heidelberg Institute of Public Health, University Hospitals, Ruprecht-Karls-Universität, Heidelberg, Germany. Electronic address: philipp.zanger@uni-heidelberg.de.
Abstract
OBJECTIVES: Toll-like receptor (TLR) 9 could have importance in human Staphylococcus aureus immunity, but population-level evidence for this hypothesis is missing. METHODS: We phenotyped S. aureus nasal carriage of 603 volunteers using four consecutive swabs, genotyped TLR9 promotor variants in 106 persistent carriers and 219 noncarriers, measured TLR9-mRNA expression in whole blood after stimulation with viable S. aureus and studied mutual associations of carriage, transcriptional activity and single nucleotide polymorphisms while accounting for sex and hormone contraceptive use (HCU). RESULTS: The -1486 (rs187084) and -1237 (rs5743836) CT haplotype was more common in noncarriers (185/438, 42%) than in carriers (63/212, 30%), with the TT haplotype showing a reverse association (noncarriers, 180/438, 41%; carriers 117/212, 55%) (χ2 p 0.001). Mean TLR9 mRNA expression in whole blood was higher in noncarriers (ratiocarriers/noncarriers 0.63; 95% confidence interval, 0.43-0.92; p 0.017). A duplication of TLR9 transcriptional activity lowered the odds of persistent S. aureus carriage by 37% in the overall group (odds ratio = 0.63; 95% confidence interval, 0.42-0.94; p 0.022) and by 54% in women (odds ratio = 0.46; 95% confidence interval, 0.23-0.90; p 0.023). Promotor haplotype and HCU had a combined effect on TLR9 transcription (interaction model): women in the TT (risk) haplotype/HCU- stratum (baseline) had lower mRNA levels than women in the CT (protective) haplotype/HCU- (ratio 1.92; p 0.055), the CT haplotype/HCU+ (ratio 2.02; p 0.032) and the TT haplotype/HCU+ (ratio 2.59; p < 0.004) strata. No such associations were observed in men. CONCLUSIONS: We provide evidence that TLR9 affects human S. aureus immunity and present potential explanations for differences according to sex in S. aureus colonization and infection.
OBJECTIVES: Toll-like receptor (TLR) 9 could have importance in humanStaphylococcus aureus immunity, but population-level evidence for this hypothesis is missing. METHODS: We phenotyped S. aureus nasal carriage of 603 volunteers using four consecutive swabs, genotyped TLR9 promotor variants in 106 persistent carriers and 219 noncarriers, measured TLR9-mRNA expression in whole blood after stimulation with viable S. aureus and studied mutual associations of carriage, transcriptional activity and single nucleotide polymorphisms while accounting for sex and hormone contraceptive use (HCU). RESULTS: The -1486 (rs187084) and -1237 (rs5743836) CT haplotype was more common in noncarriers (185/438, 42%) than in carriers (63/212, 30%), with the TT haplotype showing a reverse association (noncarriers, 180/438, 41%; carriers 117/212, 55%) (χ2 p 0.001). Mean TLR9 mRNA expression in whole blood was higher in noncarriers (ratiocarriers/noncarriers 0.63; 95% confidence interval, 0.43-0.92; p 0.017). A duplication of TLR9 transcriptional activity lowered the odds of persistent S. aureus carriage by 37% in the overall group (odds ratio = 0.63; 95% confidence interval, 0.42-0.94; p 0.022) and by 54% in women (odds ratio = 0.46; 95% confidence interval, 0.23-0.90; p 0.023). Promotor haplotype and HCU had a combined effect on TLR9 transcription (interaction model): women in the TT (risk) haplotype/HCU- stratum (baseline) had lower mRNA levels than women in the CT (protective) haplotype/HCU- (ratio 1.92; p 0.055), the CT haplotype/HCU+ (ratio 2.02; p 0.032) and the TT haplotype/HCU+ (ratio 2.59; p < 0.004) strata. No such associations were observed in men. CONCLUSIONS: We provide evidence that TLR9 affects human S. aureus immunity and present potential explanations for differences according to sex in S. aureus colonization and infection.
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: Clarissa Leal Silva E Souza; Camila Dutra Barbosa; Hanna I L N Coelho; Manoel N Santos Júnior; Elaine Novaes Barbosa; Éllunny Chaves Queiroz; Mauro Fernandes Teles; Déborah Cruz Dos Santos; Rafaela Souza Bittencourt; Telma de Jesus Soares; Márcio Vasconcelos Oliveira; Jorge Timenetsky; Guilherme Barreto Campos; Lucas Miranda Marques Journal: Front Cell Infect Microbiol Date: 2021-07-14 Impact factor: 5.293