PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan

Kaneko, Takashi; Yano, Tamaki; Aggarwal, Kamna; Lim, Jae Hong; Ueda, Kazunori; Oshima, Yoshiteru; Peach, Camilla; Ertürk-Hasdemir, Deniz; Goldman, William E.; Oh, Byung Ha; Kurata, Shoichiro; Silverman, Neal S.

doi:10.1038/ni1356

Cited by 350 publications

(358 citation statements)

References 32 publications

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“…17,18) In contrast, meso-diaminopimelic acid-containing PGNs (DAP-type PGNs) from Gram-negative bacteria and a subclass of Gram-positive bacteria, which includes Bacillus species, have been reported to stimulate the IMD pathway through PGN recognition proteins, PGRP-LC and PGRP-LE. 19) Extracellular factors involved in the Toll pathway, such as Necrotic and Persephone, 20,21) and intercellular factors for the Toll and IMD pathways, have also been identified, 4,5) although further study is needed to understand these pathways further.…”

Section: Bombyx Morimentioning

confidence: 99%

Correlation of Differential Expression of Silkworm Antimicrobial Peptide Genes with Different Amounts of Rel Family Proteins and Their Gene Transcriptional Activity

Tanaka

Sagisaka

Nakajima

et al. 2009

Bioscience, Biotechnology, and Biochemistry

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Section: Bombyx Morimentioning

confidence: 99%

Correlation of Differential Expression of Silkworm Antimicrobial Peptide Genes with Different Amounts of Rel Family Proteins and Their Gene Transcriptional Activity

Tanaka

Sagisaka

Nakajima

et al. 2009

Bioscience, Biotechnology, and Biochemistry

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“…Imd interacts directly with both PGRP-LC or -LE receptors (4), as well as with the Drosophila FADD homolog, which in turn recruits the caspase-8-like Dredd (5,6). Upon PGN stimulation, Imd is endoproteolytic cleaved, at aspartate residue 30 within a caspase recognition site.…”

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confidence: 99%

The Caspase-8 Homolog Dredd Cleaves Imd and Relish but Is Not Inhibited by p35

Kim

Paik

Rus

et al. 2014

Journal of Biological Chemistry

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Background: During the Drosophila immune response, both Imd and Relish are cleaved in a manner dependent on the caspase-8 homolog Dredd. Results: Dredd cleaves Imd and Relish, but not the caspase inhibitor p35, without interdomain autoprocessing. Conclusion: Imd and Relish are direct substrates for full-length Dredd. Significance: Dredd is similar to some mammalian initiator caspases, which can function without interdomain cleavage.In Drosophila, the Imd pathway is activated by diaminopimelic acid-type peptidoglycan and triggers the humoral innate immune response, including the robust induction of antimicrobial peptide gene expression. Imd and Relish, two essential components of this pathway, are both endoproteolytically cleaved upon immune stimulation. Genetic analyses have shown that these cleavage events are dependent on the caspase-8 like Dredd, suggesting that Imd and Relish are direct substrates of Dredd. Among the seven Drosophila caspases, we find that Dredd uniquely promotes Imd and Relish processing, and purified recombinant Dredd cleaves Imd and Relish in vitro. In addition, interdomain cleavage of Dredd is not required for Imd or Relish processing and is not observed during immune stimulation. Baculovirus p35, a suicide substrate of executioner caspases, is not cleaved by purified Dredd in vitro. Consistent with this biochemistry but contrary to earlier reports, p35 does not interfere with Imd signaling in S2* cells or in vivo.The Imd pathway is one of two NF-B signaling pathways controlling antimicrobial peptide (AMP) 4 induction in the Drosophila immune response. Diaminopimelic acid-type peptidoglycan (PGN), from Gram-negative and some Gram-positive bacteria, stimulates the Imd pathway through receptors PGRP-LC and PGRP-LE, and leads to the activation of Relish, a NF-B precursor protein similar to mammalian p100 and p105. Unlike p100 or p105 processing, Relish is activated by endoproteolytic cleavage, and then translocates to the nucleus where it drives robust (100-fold or more) AMP gene expression (recently reviewed in Refs. 1 and 2).In this pathway, the Imd protein plays a central role as receptor proximal adapter (3). Imd interacts directly with both PGRP-LC or -LE receptors (4), as well as with the Drosophila FADD homolog, which in turn recruits the caspase-8-like Dredd (5, 6). Upon PGN stimulation, Imd is endoproteolytic cleaved, at aspartate residue 30 within a caspase recognition site. Genetic studies demonstrated that this signal-induced cleavage is dependent on Fadd and Dredd. Once cleaved, Imd exposes a new N terminus that contains inhibitor of apoptosis binding motif. The E3 ubiquitin ligase Iap2 associates with cleaved Imd through the newly exposed inhibitor of apoptosis binding motif, and rapidly conjugates Imd with K63-linked polyubiquitin. K63 polyubiquitin chains are suggested to function as a scaffold to activate Tak1 and IKK kinases (Ird5 and Kenny), which are critical for Relish activation and AMP gene induction (7).In the absence of immune stimulation, Relish is found in the c...

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“…PGRP-LE, first reported by our group to be an extracellular bacteria recognition protein, exists in both the hemolymph and inside hemocytes, the immune reactive cells, and can activate immune signaling in response to a bacterial component inside cultured cells. [13][14][15] These findings led us to examine the function of PGRP-LE as a recognition receptor for intracellular bacteria, and to further study PGRP-LE mediated innate immune responses against intracellular bacteria.…”

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confidence: 99%