RRC ID 47426
Author Iatsenko I, Kondo S, Mengin-Lecreulx D, Lemaitre B.
Title PGRP-SD, an Extracellular Pattern-Recognition Receptor, Enhances Peptidoglycan-Mediated Activation of the Drosophila Imd Pathway.
Journal Immunity
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.
Volume 45(5)
Pages 1013-1023
Published 2016-11-15
DOI 10.1016/j.immuni.2016.10.029
PII S1074-7613(16)30440-X
PMID 27851910
MeSH Animals Carrier Proteins / immunology* Disease Models, Animal Drosophila Proteins / immunology* Drosophila melanogaster / immunology* Gram-Negative Bacterial Infections / immunology* Immunity, Innate / immunology Myogenic Regulatory Factors / immunology* Peptidoglycan / immunology Polymerase Chain Reaction Receptors, Pattern Recognition / immunology Signal Transduction / immunology*
IF 21.522
Times Cited 4