Abstract
P>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 endotoxinlow 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 endotoxinlow 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 endotoxinlow 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.
Cite this as: S. Phipps, N. Hansbro, C. E. Lam, S. Y. Foo, K. I. Matthaei and P. S. Foster, Clinical & Experimental Allergy, 2009 (39) 1920-1928.