Through continued NIH-funding, we are presently involved in studies investigating the role that innate immunity plays in modulating allergic reactions. These studies also focus on the use of basophils and mast cells, and have additionally incorporated investigations probing the biology of specific dendritic cells that express IgE receptors. Particular emphasis relates to the Toll-Like Receptors (TLR) found on these cells and how microbial-derived ligands interacting with these receptors induce phenotypic changes and modify the function in these cells. We were among the first to demonstrate that human basophils are a significant source of IL-4/IL-13 -the allergy-promoting cytokines originally thought to be made only by T cells. Our recent progress has also revealed evidence for counter-regulation between TLR7/9 vs. IgE receptor signaling, which potentially provides insight into molecular mechanisms linked to the Hygiene Hypothesis. These in vitro studies are also highly connected to our ongoing collaborations with clinical colleagues, whereby we are actively investigate mechanisms underlying the efficacy of a novel therapeutic modalities (e.g. CpG oligodeoxynucleotide-based vaccines and oral/sublingual immunotherapy) in the treatment of allergic disease.