Immune response is broadly categorized into innate and acquired immunity. Acquired immunity is mediated by T and B cells, both of which generate their receptors through DNA rearrangement and respond to a wide range of potential antigens. This highly sophisticated system is observed only in vertebrates and has been the subject of considerable study in the past century. On the other hand, innate immunity is phylogenetically conserved and was formerly considered as non-specific because the major work of this system is to digest pathogens and present the antigen to the cells involved in acquired immunity. Therefore, the study on innate immunity has been for a long time discarded and not appreciated. However, recent studies (that started just a few years ago) showed that innate immunity is not non-specific but specific enough to discriminate self and pathogens through evolutionarily conserved receptors, named Toll-like receptors (TLRs) that play a crucial role in early host defense against invading pathogens. Furthermore, accumulating evidence indicates that activation of innate immunity is prerequisite to induction of acquired immunity. This Copernican revolution of the concept of immune system is now changing our thinking on pathogenesis and treatment of infectious diseases, immune diseases, allergic diseases, and cancers.

Our group has been studying the roles of Toll-like receptors, and the signaling mainly by generating the knockout mice and analyzing them. In this concise review article we summarized recent progress on TLRs, focusing on the immunological aspects of the role of TLRs as well as the signaling pathways more than the previous reviews.