The invention relates to compositions and methods related to Toll-like receptor (TLR) polypeptides. In some embodiments, the invention relates to managing TLR3 related diseases. In further embodiments, the invention relates to methods of preventing and treating inflammation. In some embodiments, the invention relates to antagonists of TLR3, to amino acid sequences that act as dominant negative molecules, and to nucleic acid sequences that encode said amino acid sequences. In additional embodiments, the invention relates to the manipulation of biological materials to evaluate TLR3 activity.