A Novel Toll-Like Receptor That Recognizes Bacterial DNA

In mammalian immune system, activation of innate immunity is crucial for protecting the host from invading pathogens. The innate immune system specifically recognizes structural patterns of microbial components, which are conserved among a wide variety of microorganisms. These structural patterns are termed pathogen associated molecular patters (PAMPs), and include lipopolysaccharide (LPS), peptidoglycan (PGN), bacterial lipoproteins (BLP), mannans, and bacterial DNA (1). All of these are essential for the microbe’s survival and are not expressed on the host. The host immune system has developed the receptors that can specifically recognize PAMPs, so-called pattern recognition receptors (PRRs). As one of PRRs, Toll-like receptor (TLR) family has been well studied (2,3). TLR family has been phylogenetically conserved from insects to mammals and characterized as a type I transmembrane protein with leucine-rich repeats in the extracellular domain and a cytoplasmic Toll/interleukin (IL)-1 receptor homology (TIR) domain. So far, ten members of human TLR are identified (2). Biological functions of some TLR family members are revealed; TLR4 is responsible for the recognition of LPS and TLR2 is involved in that of PGN and BLP (3). The activation of TLRs induces recruitment of the adaptor protein MyD88 and sequential activation of signaling molecules such as IRAK (IL-1 receptor associated kinase) and TRAF6 (TNF receptor associated factor).