title: Monomeric and polymeric gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway.
abstract: Insects depend solely upon innate immune responses to survive infection. These responses include the activation of extracellular protease cascades, leading to melanization and clotting, and intracellular signal transduction pathways inducing antimicrobial peptide gene expression. In Drosophila, the IMD pathway is required for antimicrobial gene expression in response to gram-negative bacteria. The exact molecular component(s) from these bacteria that activate the IMD pathway remain controversial. We found that highly purified LPS did not stimulate the IMD pathway. However, lipid A, the active portion of LPS in mammals, activated melanization in the silkworm Bombyx morii. On the other hand, the IMD pathway was remarkably sensitive to polymeric and monomeric gram-negative peptidoglycan. Recognition of peptidoglycan required the stem-peptide sequence specific to gram-negative peptidoglycan and the receptor PGRP-LC. Recognition of monomeric and polymeric peptidoglycan required different PGRP-LC splice isoforms, while lipid A recognition required an unidentified soluble factor in the hemolymph of Bombyx morii.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.forename: William E
authors.initials: WE
authors.lastname: Goldman
authors.forename: Peter
authors.initials: P
authors.lastname: Mellroth
authors.forename: Håkan
authors.initials: H
authors.lastname: Steiner
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kusumoto
authors.forename: William
authors.initials: W
authors.lastname: Harley
authors.forename: Alvin
authors.initials: A
authors.lastname: Fox
authors.forename: Douglas
authors.initials: D
authors.lastname: Golenbock
authors.forename: Neal
authors.initials: N
authors.lastname: Silverman
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D012831:Bombyx / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D004330:Drosophila / Q000276:immunology*; D029721:Drosophila Proteins / Q000276:immunology*; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000276:immunology; D008050:Lipid A / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D010457:Peptidoglycan / Q000737:chemistry / Q000276:immunology*; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D008050:Lipid A; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D020033:Protein Isoforms; C439909:imd protein, Drosophila; C118897:peptidoglycan recognition protein