Medline ® Abstracts for References 1,2,4

Innate immunity provides a first line of host defence against infection through microbial recognition and killing while simultaneously activating a definitive adaptive immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition and function mainly by detection of structural patterns that do not exist in the host. TLR2 and TLR4 were the first members of this innate immune receptor family to be strongly implicated in antibacterial host defence. Following the initial description of the mammalian TLR family, susceptibility to infection with numerous human microbial pathogens has been intensively studied using mice with engineered deletions of each of these molecules. While it has become quite clear that TLR activation is necessary for optimal host defence, a comprehensive understanding of the mechanisms by which this family of pattern recognition receptors engages protective immunity, particularly the adaptive response, is still evolving.

Toll-like receptors (TLRs) are evolutionarily conserved innate receptors expressed in various immune and non-immune cells of the mammalian host. TLRs play a crucial role in defending against pathogenic microbial infection through the induction of inflammatory cytokines and type I interferons. Furthermore, TLRs also play roles in shaping pathogen-specific humoral and cellular adaptive immune responses. In this review, we describe the recent advances in pathogen recognition by TLRs and TLR signaling.

Mammals sense pathogen invasion through pattern-recognition receptors. A group of transmembrane proteins, Toll-like receptors (TLRs), play critical roles as pattern-recognition receptors. They are mainly expressed on antigen-presenting cells, such as macrophages or dendritic cells, and their signaling activates antigen-presenting cells to provoke innate immunity and to establish adaptive immunity. Each TLR has common effects, such as inflammatory cytokine induction or upregulation of costimulatory molecule expression, but also has its specific function, exemplified by type I IFN-inducing ability. These immunoadjuvant effects are not only critical in antimicrobial immunity but are also involved in manifestations of autoimmunity. Furthermore, some TLR agonists are now promising therapeutic tools for various immune disorders, including allergy. Therefore understanding molecular mechanisms on TLRs should be quite useful in the development of therapeutic maneuvers against allergy and autoimmune diseases.