title: Allergic sensitization is enhanced in early life through toll-like receptor 7 activation.
abstract: BACKGROUND
  Prospective cohort studies suggest that children hospitalized in early life with severe infections are significantly more likely to develop recurrent wheezing and asthma.
  
  
  OBJECTIVE
  Using an inhalational mouse model of allergic airways inflammation, we sought to determine the effect of viral and bacterial-associated molecular patterns on the magnitude of the allergic inflammatory response and whether this effect was age dependent.
  
  
  METHODS
  BALB/c mice were sensitized by intranasal administration of endotoxin(low) ovalbumin (OVA) in the absence or presence of viral single-stranded (ss)RNA, lipoteichoic acid or flagellin as neonates (within the first 24 h of life) or as weanlings (4 weeks of age). Mice were challenged four times with OVA at 6 weeks of age and end-points (bronchoalveolar lavage cytology, histology, antigen-specific T and B cell responses) determined at 7 weeks of age.
  
  
  RESULTS
  Inhalational sensitization (<24 h or 4 weeks of age) and challenge with OVA induced a mild allergic inflammatory response in the airways as indicated by increased numbers of eosinophils and mucus cells, elevated serum OVA-specific IgG1, and production of T helper 2 (Th2) cytokines. Mice sensitized to endotoxin(low) OVA at birth in the presence of ssRNA or lipoteichoic acid, but not flagellin, showed an increase in the numbers of airway and tissue eosinophils, mucus producing cells and antigen-specific production of IL-13 as compared with mice exposed only to endotoxin(low) OVA. By contrast, all three TLR ligands failed to increase the magnitude of OVA-induced allergic inflammation in mice sensitized as weanlings.
  
  
  CONCLUSIONS
  Recognition of distinct microbial-associated patterns in early life may preferentially promote the de novo differentiation of bystander, antigen-specific CD4(+) T cells toward a Th2 phenotype, and promote an asthma-like phenotype upon cognate antigen exposure in later life.
authors.affiliation: Centre for Asthma and Respiratory Diseases (CARD) and Hunter Medical Research Institute (HMRI), School of Biomedical Sciences, University of Newcastle, Newcastle, NSW, Australia. simon.phipps@newcastle.edu.au
authors.forename: S
authors.initials: S
authors.lastname: Phipps
authors.forename: N
authors.initials: N
authors.lastname: Hansbro
authors.forename: C E
authors.initials: CE
authors.lastname: Lam
authors.forename: S Y
authors.initials: SY
authors.lastname: Foo
authors.forename: K I
authors.initials: KI
authors.lastname: Matthaei
authors.forename: P S
authors.initials: PS
authors.lastname: Foster
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004802:Eosinophilia / Q000473:pathology; D005408:Flagellin / Q000494:pharmacology; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006965:Hyperplasia / Q000473:pathology; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012367:RNA, Viral / Q000494:pharmacology; D013682:Teichoic Acids / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051199:Toll-Like Receptor 7 / Q000502:physiology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D018793:Interleukin-13; D015848:Interleukin-5; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; C477038:Tlr7 protein, mouse; D051195:Toll-Like Receptor 2; D051199:Toll-Like Receptor 7; D005408:Flagellin; D015847:Interleukin-4; C009900:lipoteichoic acid; D007371:Interferon-gamma; D010047:Ovalbumin