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PGRP-SD, an Extracellular Pattern-Recognition Receptor, Enhances Peptidoglycan-Mediated Activation of the Drosophila Imd Pathway.

Immunity. 2016 Nov 15;45(5):1013-1023
Igor Iatsenko 1 , Shu Kondo 2 , Dominique Mengin-Lecreulx 3 , Bruno Lemaitre 4
Igor Iatsenko 1 , Shu Kondo 2 , Dominique Mengin-Lecreulx 3 , Bruno Lemaitre 4

[No authors listed]

Author information
  • 1 Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland. Electronic address: igor.iatsenko@epfl.ch.
  • 2 Invertebrate Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, Mishima 411-8540, Japan.
  • 3 Institute for Integrative Biology of the Cell, CEA, CNRS, Univ Paris-Sud and Université Paris-Saclay, 91198, Gif-sur-Yvette Cedex, France.
  • 4 Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland. Electronic address: bruno.lemaitre@epfl.ch.

摘要


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.