In response to pathogens and danger-associated molecules, the innate immune system initiates downstream signal transduction to produce pro-inflammatory cytokines. Allergies, atherosclerosis, auto-immune diseases, and several types of cancer result from signaling disorders of this immune response. Toll-like receptors (TLRs) dependent signaling is a well-known innate immune signaling process that can recognize pathogens and danger signals in a process called pattern recognition. The process goes through receptors and the adaptor's response. The cytosolic adaptor protein MyD88 (myeloid differentiation primary response gene 88) is used by all TLRs (1-10) except TLR3. MyD88 contains a TIR (Toll/interleukin-1 receptor/resistance protein) domain and a DD (death domain). There are several kinds of cytosolic receptor proteins that can recognize and bind to viral, bacterial and host DNA; these DNA sensor receptors (cGAS, AIM2) can catalyze the synthesis of cyclic nucleotides and activate the immune system. These receptors are good targets for some cancer and DNA vaccine studies. DNA vaccination studies show that overexpression of MyD88 adaptor protein improves DNA vaccine immunogenicity in vitro. Our studies suggest that the cytosolic TIR domain of MyD88 also interacts with DNA to form large assemblies. We show that dsDNA can induce the higher-order assembly of MyD88 TIR domains, which may represent a new cytoplasmic DNA-induced immune pathway. Our aim is to investigate the structural basis of MyD88 TIR domain binding to dsDNA and determine the role of cytosolic DNA in TLR-mediated immune system responses. This study could open a new research field of TLR-associated innate immunity.