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Published on: October 30, 2019
PGRP-SD, an Extracellular Pattern-Recognition Receptor, Enhances Peptidoglycan-Mediated Activation of the Drosophila
Igor Iatsenko1, Shu Kondo2, Dominique Mengin-Lecreulx3
1Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland.
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.
Insights
Drosophila PGRP-SD acts as an extracellular receptor, enhancing the innate immune response to bacteria by improving peptidoglycan detection and signaling. This discovery highlights dual intra- and extracellular receptor use in bacteria detection.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Metazoan innate immunity relies on pattern-recognition receptors to detect microbes.
- In Drosophila, Gram-negative bacteria are recognized by PGRP-LC and PGRP-LE receptors.
Purpose of the Study:
- To investigate the role of PGRP-SD in Drosophila's innate immune response.
- To elucidate the mechanism by which PGRP-SD interacts with other immune receptors and bacterial components.
Main Methods:
- Mutagenesis studies of PGRP-SD.
- Analysis of Imd signaling pathway activation.
- Assays for bacterial susceptibility and peptidoglycan localization.
Main Results:
- PGRP-SD functions upstream of PGRP-LC as an extracellular receptor.
- PGRP-SD enhances peptidoglycan-mediated Imd signaling activation.
- PGRP-SD mutants show impaired immunity and increased susceptibility to specific bacteria.
- PGRP-SD promotes peptidoglycan localization to the cell surface.
- PGRP-SD antagonizes PGRP-LB, a negative regulator, to fine-tune immune response.
Conclusions:
- Drosophila PGRP-SD acts as an extracellular receptor, analogous to mammalian CD14.
- The study reveals a dual receptor system (intra- and extracellular) for bacterial detection in Drosophila.
- PGRP-SD plays a crucial role in modulating the intensity and effectiveness of the innate immune response.
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