Toll-like receptors: an overview from invertebrates to vertebrates

Abstract

Toll-like receptors (TLRs) are membrane glycoproteins consisting of an ectodomain, encompassing tandem LRRs (leucine-rich repeats), a membrane spanning segment and a globular cytoplasmic Toll/Interleukin-1 Receptor (TIR) domain. They detect microbes on the basis of conserved Pathogen-Associated Molecular Patterns (PAMPs). TLRs share molecular architecture and common ancestors with arthropod Toll molecules, which show a dual role, in the dorsoventral patterning of the embryo, and in the immune response to fungal infections in the adult. During the metazoan evolution Toll/TLRs modified the number and the arrangment of LRRs (protostome- and vertebrate-type), the localization of the loops interacting with different ligands, the ability to reside in the cellular or endosomal membrane and the complexity of the signaling pathway. The evolutionary mechanisms of Toll/TLR gene diversification included gene duplication, retrotranscription, high gene expansion rate within species, and alternative splicing of the transcripts. The aim of this review is to supply a schematic representation of a very complex, but still, fascinating story.

Keywords

• Toll-like receptor
• signaling
• pathogens recognition receptors
• TIR domain
• leucine-rich repeat
• metazoan evolution