title: PGRP-SD, an Extracellular Pattern-Recognition Receptor, Enhances Peptidoglycan-Mediated Activation of the Drosophila Imd Pathway.
abstract: Activation of the innate immune response in Metazoans is initiated through the recognition of microbes by host pattern-recognition receptors. In Drosophila, diaminopimelic acid (DAP)-containing peptidoglycan from Gram-negative bacteria is detected by the transmembrane receptor PGRP-LC and by the intracellular receptor PGRP-LE. Here, we show that PGRP-SD acted upstream of PGRP-LC as an extracellular receptor to enhance peptidoglycan-mediated activation of Imd signaling. Consistent with this, PGRP-SD mutants exhibited impaired activation of the Imd pathway and increased susceptibility to DAP-type bacteria. PGRP-SD enhanced the localization of peptidoglycans to the cell surface and hence promoted signaling. Moreover, PGRP-SD antagonized the action of PGRP-LB, an extracellular negative regulator, to fine-tune the intensity of the immune response. These data reveal that Drosophila PGRP-SD functions as an extracellular receptor similar to mammalian CD14 and demonstrate that, comparable to lipopolysaccharide sensing in mammals, Drosophila relies on both intra- and extracellular receptors for the detection of bacteria.
authors.affiliation: Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland. Electronic address: igor.iatsenko@epfl.ch.
authors.forename: Igor
authors.initials: I
authors.lastname: Iatsenko
authors.affiliation: Invertebrate Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, Mishima 411-8540, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Institute for Integrative Biology of the Cell, CEA, CNRS, Univ Paris-Sud and Université Paris-Saclay, 91198, Gif-sur-Yvette Cedex, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mengin-Lecreulx
authors.affiliation: Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland. Electronic address: bruno.lemaitre@epfl.ch.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lemaitre
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000276:immunology*; D004331:Drosophila melanogaster / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D018006:Myogenic Regulatory Factors / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology; D016133:Polymerase Chain Reaction; D051192:Receptors, Pattern Recognition / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D018006:Myogenic Regulatory Factors; D010457:Peptidoglycan; D051192:Receptors, Pattern Recognition; C442328:lmd protein, Drosophila; C118897:peptidoglycan recognition protein