Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/808573
- Allergic sensitization is enhanced in early life through toll-like receptor 7 activation
Lam, C. E.;
Foo, S. Y.;
Matthaei, K. I.;
Foster, P. S.
- The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
- 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 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 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.
- Clinical and Experimental Allergy Vol. 39, Issue 12, p. 1920-1928
- Publisher Link
- Wiley-Blackwell Publishing
- Resource Type
- journal article