Toll-like receptors in invertebrate innate immunity

Abstract

Among invertebrates, innate immunity is the only defense mechanism against harmful non-self agents.In response to recognition of microbial pattern molecules, Drosophila melanogaster activates either the Toll or Imd pathway, leading to the translocation of NF-kB (or Rel) transcription factors from the cytoplasm to the nucleus and the subsequent production of antimicrobial peptides, which provide systemic innate immunity. Toll-like receptors (TLRs) are characterized by an extracellular leucine rich repeat (LRR) domain and an intracellular Toll/interleukin-1 receptor (TIR) domain. TLRs are found from cnidarians to mammals. Here we argue that TLR mediated innate immunity developed during an early stage of evolution when organisms acquired a body cavity. This is supported by the distributions of TLR and Rel genes in the animal kingdom. Further, TLR mediated immunity appears to have developed independently in invertebrates and vertebrates. Recent studies have shown that microbial molecules, with the potential to signal through TLR, can be beneficial to host survival. Studies on this signaling pathway could open doors to a better understanding of the origins of innate immunity in invertebrates and potential transmission blocking strategies aimed at ameliorating vector-borne diseases.