PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan

Nat Immunol. 2006 Jul;7(7):715-23. doi: 10.1038/ni1356. Epub 2006 Jun 11.

Abstract

Drosophila rely entirely on an innate immune response to combat microbial infection. Diaminopimelic acid-containing peptidoglycan, produced by Gram-negative bacteria, is recognized by two receptors, PGRP-LC and PGRP-LE, and activates a homolog of transcription factor NF-kappaB through the Imd signaling pathway. Here we show that full-length PGRP-LE acted as an intracellular receptor for monomeric peptidoglycan, whereas a version of PGRP-LE containing only the PGRP domain functioned extracellularly, like the mammalian CD14 molecule, to enhance PGRP-LC-mediated peptidoglycan recognition on the cell surface. Interaction with the imd signaling protein was not required for PGRP-LC signaling. Instead, PGRP-LC and PGRP-LE signaled through a receptor-interacting protein homotypic interaction motif-like motif. These data demonstrate that like mammals, drosophila use both extracellular and intracellular receptors, which have conserved signaling mechanisms, for innate immune recognition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Bordetella pertussis / immunology
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Membrane / immunology
  • Cells, Cultured
  • Diaminopimelic Acid / immunology*
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology
  • Drosophila melanogaster / immunology*
  • Escherichia coli / immunology
  • Gene Expression Regulation
  • Hemolymph / immunology
  • Intracellular Fluid / immunology
  • Malpighian Tubules / immunology
  • Molecular Sequence Data
  • Peptide Fragments / physiology
  • Peptidoglycan / chemistry
  • Peptidoglycan / immunology*
  • RNA Interference
  • Recombinant Fusion Proteins / physiology
  • Signal Transduction / immunology
  • Transfection
  • Virulence Factors, Bordetella / chemistry
  • Virulence Factors, Bordetella / immunology*

Substances

  • Carrier Proteins
  • DptA protein, Drosophila
  • Drosophila Proteins
  • Peptide Fragments
  • Peptidoglycan
  • Recombinant Fusion Proteins
  • Virulence Factors, Bordetella
  • imd protein, Drosophila
  • peptidoglycan recognition protein
  • tracheal cytotoxin, Bordetella pertussis
  • Diaminopimelic Acid