Common human Toll-like receptor 4 polymorphisms--role in susceptibility to respiratory syncytial virus infection and functional immunological relevance

Stéphane C Paulus; Aaron F Hirschfeld; Rachel E Victor; John Brunstein; Eva Thomas; Stuart E Turvey

doi:10.1016/j.clim.2007.03.003

Common human Toll-like receptor 4 polymorphisms--role in susceptibility to respiratory syncytial virus infection and functional immunological relevance

Clin Immunol. 2007 Jun;123(3):252-7. doi: 10.1016/j.clim.2007.03.003. Epub 2007 Apr 20.

Authors

Stéphane C Paulus¹, Aaron F Hirschfeld, Rachel E Victor, John Brunstein, Eva Thomas, Stuart E Turvey

Affiliation

¹ Department of Pediatrics, BC Children's Hospital and Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.

PMID: 17449325
DOI: 10.1016/j.clim.2007.03.003

Abstract

Evidence suggests that Toll-like receptor 4 (TLR4) contributes to immune recognition of respiratory syncytial virus (RSV). The TLR4 gene harbours a polymorphism-Asp299Gly-previously associated with reduced TLR4 signalling. To understand of how host genetic variation influences the outcome of RSV infection in children, we examined the association between the TLR4 299Gly allele and severe RSV disease. By genotyping 236 children with RSV infection and 219 healthy controls we found no association between the risk of severe RSV infection and Asp299Gly polymorphisms (P>0.05), and we demonstrate that the TLR4 Asp299Gly genotype does not influence susceptibility to either RSV serotype A or B (P>0.05). Finally, examining the functional impact of the TLR4 Asp299Gly polymorphism (n=58), we demonstrate that proinflammatory cytokine production following TLR4 activation was indistinguishable between homozygous (Asp/Asp) and heterozygous (Asp/Gly) subjects. We conclude that the Asp299Gly TLR4 polymorphism does not alter receptor function and does not influence the risk of severe RSV infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Child, Preschool
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Infant
Infant, Newborn
Interleukin-1beta / metabolism
Interleukin-6 / metabolism
Leukocytes, Mononuclear / drug effects
Leukocytes, Mononuclear / immunology
Leukocytes, Mononuclear / metabolism
Lipopolysaccharides / pharmacology
Male
Polymorphism, Single Nucleotide*
Respiratory Syncytial Virus Infections / diagnosis
Respiratory Syncytial Virus Infections / genetics*
Respiratory Syncytial Virus Infections / immunology
Respiratory Syncytial Virus, Human / immunology*
Risk Factors
Toll-Like Receptor 4 / genetics*
Tumor Necrosis Factor-alpha / metabolism

Substances

Interleukin-1beta
Interleukin-6
Lipopolysaccharides
TLR4 protein, human
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha