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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Bordetella pertussis / immunology
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Membrane / immunology
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Cells, Cultured
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Diaminopimelic Acid / immunology*
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Drosophila Proteins / biosynthesis
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Drosophila Proteins / genetics
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Drosophila Proteins / physiology
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Drosophila melanogaster / immunology*
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Escherichia coli / immunology
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Gene Expression Regulation
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Hemolymph / immunology
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Intracellular Fluid / immunology
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Malpighian Tubules / immunology
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Molecular Sequence Data
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Peptide Fragments / physiology
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Peptidoglycan / chemistry
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Peptidoglycan / immunology*
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RNA Interference
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Recombinant Fusion Proteins / physiology
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Signal Transduction / immunology
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Transfection
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Virulence Factors, Bordetella / chemistry
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Virulence Factors, Bordetella / immunology*
Substances
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Carrier Proteins
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DptA protein, Drosophila
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Drosophila Proteins
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Peptide Fragments
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Peptidoglycan
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Recombinant Fusion Proteins
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Virulence Factors, Bordetella
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imd protein, Drosophila
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peptidoglycan recognition protein
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tracheal cytotoxin, Bordetella pertussis
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Diaminopimelic Acid