Origin of Toll-like receptor-mediated innate immunity

J Mol Evol. 2004 Apr;58(4):442-8. doi: 10.1007/s00239-003-2565-8.


Toll-related receptors (TLR) have been found in four animal phyla: Nematoda, Arthropoda, Echinodermata, and Chordata. No TLR has been identified thus far in acoelomates. TLR genes play a pivotal role in the innate immunity in both fruit fly and mammals. The prevailing view is that TLR-mediated immunity is ancient. The two pseudocoelomate TLRs, one each from Caenorhabditis elegans and Strongyloides stercoralis, were distinct from the coelomate ones. Further, the only TLR gene (Tol-1) in Ca. elegans did not appear to play a role in innate immunity. We argue that TLR-mediated innate immunity developed only in the coelomates, after they split from pseudocoelomates and acoelomates. We hypothesize that the function of TLR-mediated immunity is to prevent microbial infection in the body cavity present only in the coelomates. Phylogenetic analysis showed that almost all arthropod TLRs form a separate cluster from the mammalian counterparts. We further hypothesize that TLR-mediated immunity developed independently in the protostomia and deuterostomia coelomates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cluster Analysis
  • DNA
  • Exons
  • Immunity, Innate / physiology*
  • Introns
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / physiology*
  • Molecular Sequence Data
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / physiology*
  • Toll-Like Receptors


  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • DNA