Toll-like receptor 2 and 4 in cockroach antigen-induced asthma: a potential mechanism for establishing a Th1 phenotype (79.23)

Abstract

Abstract According to the hygiene hypothesis, sensing bacteria in the gut is imperative to switching the immune system from Th2 to Th1, thus reducing potential for an asthma-like phenotype developing in the lungs. In the gut toll-like receptors 2 and 4 (TLR2, TLR4) are critical for sensing Gram positive and negative bacteria, respectively. Previous data indicate in the first two weeks of life when the immune system switch generally occurs and a microbial repertoire is established, these two receptors are significantly upregulated. This project's hypothesis is TLR2 and 4 are critical for microbial sensing in the gut, thus C57BL/6 mice deficient in TLR2, TLR4, or both (double knockout) should have a more asthmatic phenotype. Interestingly, after inducing asthma with cockroach antigen (CRA) in a specific pathogen-free environment, the TLR2-/-/4-/- treated with CRA had a significant increase in serum IgE compared to the C57BL/6 treated with CRA, while the TLR4-/- had increased IL-13 mRNA levels compared to the C57BL/6 treated with CRA. This indicates the lack of interplay of TLR2 and 4 may play a role in maintaining a Th2 phenotype in the lungs; consequently preventing the immune switch to a Th1 phenotype. Research supported by the Strategic Program for Asthma Research