Toll-like receptor (TLR) family acts as pattern recognition receptors for pathogen-specific molecular patterns. We previously showed that TLR2 recognizes Gram-positive bacterial components whereas TLR4 recognizes LPS, a component of Gram-negative bacteria. MyD88 is shown to be an adaptor molecule essential for TLR family signaling. To investigate the role of TLR family in host defense against Gram-positive bacteria, we infected TLR2- and MyD88-deficient mice with Staphylococcus aureus. Both TLR2- and MyD88-deficient mice were highly susceptible to S. aureus infection, with more enhanced susceptibility in MyD88-deficient mice. Peritoneal macrophages from MyD88-deficient mice did not produce any detectable levels of cytokines in response to S. aureus. In contrast, TLR2-deficient macrophages produced reduced, but significant, levels of the cytokines, and TLR4-deficient macrophages produced the same amounts as wild-type cells, indicating that S. aureus is recognized not only by TLR2, but also by other TLR family members except for TLR4.
No abstract is provided for this article.
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.
