title: PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan.
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.
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Tamaki
authors.initials: T
authors.lastname: Yano
authors.forename: Kamna
authors.initials: K
authors.lastname: Aggarwal
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Lim
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ueda
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Oshima
authors.forename: Camilla
authors.initials: C
authors.lastname: Peach
authors.forename: Deniz
authors.initials: D
authors.lastname: Erturk-Hasdemir
authors.forename: William E
authors.initials: WE
authors.lastname: Goldman
authors.forename: Byung-Ha
authors.initials: BH
authors.lastname: Oh
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kurata
authors.forename: Neal
authors.initials: N
authors.lastname: Silverman
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D003960:Diaminopimelic Acid / Q000276:immunology*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D004331:Drosophila melanogaster / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D005786:Gene Expression Regulation; D006458:Hemolymph / Q000276:immunology; D007424:Intracellular Fluid / Q000276:immunology; D008317:Malpighian Tubules / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000502:physiology; D010457:Peptidoglycan / Q000737:chemistry / Q000276:immunology*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; C054756:DptA protein, Drosophila; D029721:Drosophila Proteins; D010446:Peptide Fragments; D010457:Peptidoglycan; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; C439909:imd protein, Drosophila; C118897:peptidoglycan recognition protein; C059708:tracheal cytotoxin, Bordetella pertussis; D003960:Diaminopimelic Acid