MyD88-deficient Hydra reveal an ancient function of TLR signaling in sensing bacterial colonizers

Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19374-9. doi: 10.1073/pnas.1213110109. Epub 2012 Oct 29.

Abstract

Toll-like receptor (TLR) signaling is one of the most important signaling cascades of the innate immune system of vertebrates. Studies in invertebrates have focused on the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, and there is little information regarding the evolutionary origin and ancestral function of TLR signaling. In Drosophila, members of the Toll-like receptor family are involved in both embryonic development and innate immunity. In C. elegans, a clear immune function of the TLR homolog TOL-1 is controversial and central components of vertebrate TLR signaling including the key adapter protein myeloid differentiation primary response gene 88 (MyD88) and the transcription factor NF-κB are not present. In basal metazoans such as the cnidarians Hydra magnipapillata and Nematostella vectensis, all components of the vertebrate TLR signaling cascade are present, but their role in immunity is unknown. Here, we use a MyD88 loss-of-function approach in Hydra to demonstrate that recognition of bacteria is an ancestral function of TLR signaling and that this process contributes to both host-mediated recolonization by commensal bacteria as well as to defense against bacterial pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Base Sequence
  • Colony Count, Microbial
  • Disease Susceptibility / immunology
  • Disease Susceptibility / microbiology
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gene Knockdown Techniques
  • Hydra / drug effects
  • Hydra / genetics
  • Hydra / immunology*
  • Hydra / microbiology*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Myeloid Differentiation Factor 88 / deficiency*
  • Myeloid Differentiation Factor 88 / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation / drug effects
  • Pseudomonas Infections / immunology
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development*
  • RNA, Ribosomal, 16S / genetics
  • Sequence Analysis, RNA
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Toll-Like Receptors / drug effects
  • Toll-Like Receptors / immunology*

Substances

  • Anti-Bacterial Agents
  • Myeloid Differentiation Factor 88
  • RNA, Ribosomal, 16S
  • Toll-Like Receptors
  • JNK Mitogen-Activated Protein Kinases

Associated data

  • GEO/GSE32383