Protein family review
This in an extract of a protein family review which first appeared in GenomeBiology, and is reproduced by permission of the publisher, BioMedCentral Ltd.
Authors:
Pulmonary Center, Boston University School of Medicine, Boston, MA 02118-2394, USA
Correspondence:
Matthew J Fenton.
Email:
mfenton@bu.edu
Read the full article
Subscribers to GenomeBiology may view the full version of this review article online at www.genomebiology.com
Published:
29 July 2002
Toll-like receptors: a family of pattern-recognition receptors in mammals
Summary
The innate immune system uses a variety of germline-encoded pattern-recognition receptors that recognize conserved microbial structures or pathogen-associated molecular patterns, such as those that occur in the bacterial cell-wall components peptidoglycan and lipopolysaccharide. Recent studies have highlighted the importance of Toll-like receptors (TLRs) as a family of pattern-recognition receptors in mammals that can discriminate between chemically diverse classes of microbial products. First identified on the basis of sequence similarity with the Drosophila protein Toll, TLRs are members of an ancient superfamily of proteins, which includes related proteins in invertebrates and plants. TLRs activate innate immune defense reactions, such as the release of inflammatory cytokines, but increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The sequence similarity between the intracellular domains of the TLRs and the mammalian interleukin-1 and interleukin-18 cytokine receptors reflects the use of a common intracellular signal-transduction cascade triggered by these receptor classes. But more recent findings have demonstrated that there are in fact TLR-specific signaling pathways and cellular responses. Thus, TLRs function as sentinels of the mammalian immune system that can discriminate between diverse pathogen-associated molecular patterns and then elicit pathogen-specific cellular immune responses.
Frontiers
It is clear that engagement of TLRs activates a variety of inflammatory and innate immune responses in mammals. Ongoing efforts in many laboratories have led to the identification of TLR-specific signaling components and cellular responses, and more will be discovered in the future. It is also likely that TLRs work in combination with additional pattern-recognition receptors and co-receptors to add further diversity to their functions in vivo. How the host integrates the information that is signaled through TLRs and any co-receptors will ultimately control the progression of the immune response to pathogens. Understanding this process will undoubtedly lead to the development of novel therapeutics and immune adjuvants.
© BioMedCentral Ltd. Protein family reviews appear as regular features in GenomeBiology. A complete list of protein family reviews is available online at http://genomebiology.com/proteinfamilyreviews/
Structural features of human members of the TLR protein family and the archetypal Drosophila Toll protein 
TLR signal transduction pathways