Innate immune recognition of nucleic acids: Beyond toll-like receptors

During infection or tissue damage, the innate immune system detects and responds to nucleic acids released from pathogens or damaged host cells. Accumulating evidence has showed that specific sequences, modifications or structures of nucleic acids influence their immunomodulatory activities. Resulting innate immune modulations are regulated by Toll-like receptor (TLR)-dependent or -independent signaling pathways. The first step in host defense against foreign or unwelcome self nucleic acids may play important roles in immune responses against infectious organisms, as well as in clearance of unnecessary tissues, which may be linked to autoimmune diseases and possibly to other immunological disorders. Elucidating mechanisms of innate immune activation by nucleic acids will help future development of more efficient or safer nucleic acid-based immunotherapies and gene therapies. © 2005 Wiley-Liss, Inc.