title: Pattern recognition receptor responses in children with chronic hepatitis B virus infection.
abstract: BACKGROUND
  Several studies have demonstrated that hepatitis B virus (HBV) affects the expression and function of Toll like receptors (TLRs), but data on TLR function in HBV infection are mainly from adult patients. The natural history of chronic hepatitis B (CHB) infection is distinctly different in children, since 90% of children become chronic carriers compared to 5% of adults when infected with HBV.
  
  
  OBJECTIVE
  We wanted to study the function of TLRs and cytosolic DNA receptors in children with CHB infection compared to healthy children.
  
  
  METHODS
  PBMCs from 19 children with CHB and 19 healthy children were stimulated with ligands for TLR 2, 3, 4, 7 and 9 for 24 h. For activation of cytosolic DNA receptors, cells were transfected with a double-stranded DNA using Lipofectamine 2000. Supernatants were analyzed for levels of IFN-α, TNF-α, IL-6, CXCL10 and CCL3 by Luminex.
  
  
  RESULTS
  Stimulation with ligands for TLR2, TLR3 and TLR9 induced IL-6, CCL3 and CXCL10 to a significantly higher level in children with CHB compared to healthy children. CHB patients displayed significantly lower IFN-α production compared to healthy children after stimulation with ligands for TLR2, TLR3 and TLR4. Stimulation of intracellular DNA sensors with synthetic double-stranded DNA elicited significantly higher induction of the inflammatory cytokines and chemokines IL-6, TNF-α and CCL3 in the CHB patients as compared to the healthy children.
  
  
  CONCLUSIONS
  Our results indicate a TLR-mediated inflammatory response in children with CHB infection. Furthermore, our study is the first to show that the responses of intracellular DNA receptors are affected in CHB.
authors.affiliation: Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Kettegaard Allé 30, 2650 Hvidovre, Denmark. Ida.heiberg@gmail.com
authors.forename: Ida Louise
authors.initials: IL
authors.lastname: Heiberg
authors.forename: Thilde Nordmann
authors.initials: TN
authors.lastname: Winther
authors.forename: Søren Riis
authors.initials: SR
authors.lastname: Paludan
authors.forename: Birthe
authors.initials: B
authors.lastname: Hogh
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000276:immunology; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D014162:Transfection
chemical_list: D016207:Cytokines; D051192:Receptors, Pattern Recognition; D004247:DNA