title: TLR3 in human eosinophils: functional effects and decreased expression during allergic rhinitis.
abstract: OBJECTIVE
  Viral respiratory infections are increasingly implicated in allergic exacerbations. Virus-induced activation of eosinophils through Toll-like receptors (TLRs) could be involved. The present study was designed to examine TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB) during symptomatic allergic rhinitis, and to evaluate the functional responsiveness of TLR3 in purified eosinophils.
  
  
  METHODS
  BM and PB samples were obtained from healthy volunteers and patients with seasonal allergic rhinitis outside and during the pollen season. Eosinophils were analyzed for TLR3 expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an agonist for TLR3, was used to assess its functional role in purified eosinophils and the intracellular signaling pathways involved.
  
  
  RESULTS
  TLR3 expression was demonstrated in BM and PB eosinophils. It was higher in BM-derived than in circulating cells and it was downregulated in both compartments during symptomatic allergic rhinitis. TLR3 expression was also downregulated in the presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects mediated via the p38 mitogen-activated protein kinases and nuclear factor-kappaB signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)-induced IL-8 release.
  
  
  CONCLUSIONS
  Eosinophils activated via TLR3 might be more able to home and recruit leukocytes to sites of inflammation. The decreased TLR3 expression during symptomatic allergic rhinitis and in the presence of Th2 cytokines indicates a role in allergic airway inflammation. Thus, eosinophils might function as a link between viral infections and exacerbations of allergic disease.
authors.affiliation: Laboratory of Clinical and Experimental Allergy Research, Department of Otorhinolaryngology Malmo University Hospital, Lund University, Malmo, Sweden.
authors.forename: Anne
authors.initials: A
authors.lastname: Månsson
authors.forename: Mattias
authors.initials: M
authors.lastname: Fransson
authors.forename: Mikael
authors.initials: M
authors.lastname: Adner
authors.forename: Mikael
authors.initials: M
authors.lastname: Benson
authors.forename: Rolf
authors.initials: R
authors.lastname: Uddman
authors.forename: Sven
authors.initials: S
authors.lastname: Björnsson
authors.forename: Lars-Olaf
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D000328:Adult; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000166:cytology; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology*; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D015853:Cysteine Proteinase Inhibitors; C508598:IL4 protein, human; C508599:IL5 protein, human; C509295:ITGAM protein, human; D007093:Imidazoles; D015848:Interleukin-5; D016209:Interleukin-8; D007976:Leupeptins; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D015847:Interleukin-4; D048051:p38 Mitogen-Activated Protein Kinases; D011070:Poly I-C; C093642:SB 203580; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde