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  • Print publication year: 2007
  • Online publication date: August 2009

2 - Toll-like receptor signaling

from I - Dendritic cells and their role in immunity

Summary

INTRODUCTION

Toll-like receptors (TLRs) play essential roles in innate immune responses. The name TLR is derived from a Drosophila protein, Toll, which detects fungal infection in the fruit fly. The immune system in Drosophila is entirely dependent on a limited number of germline-encoded receptors for pathogen recognition. In contrast, the vertebrate immune system is characterized by the evolution of acquired immunity in addition to innate immunity. Acquired immunity is mediated by T and B cells, which utilize rearranged receptors. This system is advantageous for detecting pathogens with high specificity, eradicating infection in the late stages and establishing an immunological memory. However, the mammalian innate immune system plays critical roles in the initial defense against invading pathogens and subsequent activation of the acquired immune system. Innate immune cells, such as macrophages and dendritic cells (DCs), sense pathogens through TLRs, phagocytose them and evoke immune responses.

To date, 12 different TLRs have been reported in either humans or mice. The innate immunity system targets a set of molecular structures that are unique to microorganisms and shared by various pathogens, but absent from host cells. By recognizing these “pathogen-specific” patterns, the innate immunity system is able to prevent autoimmune responses. Members of the TLR family of proteins are characterized by extracellular leucine-rich repeat (LRR) motifs responsible for ligand recognition, a transmembrane region and a cytoplasmic tail containing a Toll/IL-1 receptor homology (TIR) domain.

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