Toll-Like Receptor-1 (TLR1), TLR2 and TLR6 Gene Polymorphisms are Associated with Increased Susceptibility to Complicated Skin and Skin Structure Infections
Publication year
2014Source
Journal of Infectious Diseases, 210, (2014), pp. 311-318ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
General Internal Medicine
UMCN Extern
Medical Microbiology
Journal title
Journal of Infectious Diseases
Volume
vol. 210
Page start
p. 311
Page end
p. 318
Subject
Radboudumc 4: Infectious diseases and host response RIHS: Radboud Institute for Health Sciences; Radboudumc 4: Infectious diseases and host response RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life SciencesAbstract
Background. Complicated skin and skin structure infections (cSSSIs) are characterized by infections with either Gram-positive and Gram-negative aerobic or anaerobic bacteria, as well as a polymicrobial etiology. These invading microorganisms are recognized by pattern recognition receptors (PRRs) of the innate immune system. This study assessed whether genetic variation in genes encoding PRRs influences the susceptibility to cSSSIs.Methods. 318 cSSSI patients and 328 healthy controls were genotyped for 9 non-synonymous single nucleotide polymorphisms (SNPs) in PRR genes coding for Toll-like receptors (TLR)1/2/4/6, NOD-like receptor 2 and signaling adaptor TIRAP. PBMCs obtained from 74 SNP-genotyped healthy individuals were stimulated with Staphylococcus aureus. IL-6 cytokine concentrations were determined in supernatants by ELISA.Results. Polymorphisms in TLR1 (S248N and R80T), TLR2 (P631H) and TLR6 (P249S) increased susceptibility to cSSSIs. Furthermore, PBMCs from individuals bearing the TLR1 248N or 80T allele showed lower IL-6 secretion upon stimulation with S. aureus. No association with susceptibility to cSSSIs was observed for polymorphisms TLR2 (R753Q), TLR4 (D299G and T399I), NOD2 (P268S) and TIRAP (S180 L).Conclusions. Polymorphisms in TLR1, TLR2 and TLR6 are associated with increased susceptibility to cSSSIs. For TLR1, impaired proinflammatory cytokine production due to the polymorphism is most likely the mechanism mediating this effect.
This item appears in the following Collection(s)
- Academic publications [202914]
- Faculty of Medical Sciences [80065]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.