Publications
2021
Wehbe Layale Salem, Barakat Dana, Acker Adrian, Khoury Rita El, Reichhart Jean-Marc, Matt Nicolas, Chamy Laure El
Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the Immune Response Article de journal
Dans: J Immunol, vol. 207, no. 6, p. 1616–1626, 2021, ISSN: 1550-6606.
Résumé | Liens | BibTeX | Étiquettes: Drosophila, IKK complex, IMD, immune response, M3i, matt, NF-κB, PP4 complex
@article{pmid34452932,
title = {Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the Immune Response},
author = {Layale Salem Wehbe and Dana Barakat and Adrian Acker and Rita El Khoury and Jean-Marc Reichhart and Nicolas Matt and Laure El Chamy},
doi = {10.4049/jimmunol.1901497},
issn = {1550-6606},
year = {2021},
date = {2021-08-27},
urldate = {2021-08-27},
journal = {J Immunol},
volume = {207},
number = {6},
pages = {1616--1626},
abstract = {The evolutionarily conserved immune deficiency (IMD) signaling pathway shields against bacterial infections. It regulates the expression of antimicrobial peptides encoding genes through the activation of the NF-κB transcription factor Relish. Tight regulation of the signaling cascade ensures a balanced immune response, which is otherwise highly harmful. Several phosphorylation events mediate intracellular progression of the IMD pathway. However, signal termination by dephosphorylation remains largely elusive. Here, we identify the highly conserved protein phosphatase 4 (PP4) complex as a bona fide negative regulator of the IMD pathway. RNA interference-mediated gene silencing of , , and which encode the catalytic and regulatory subunits of the phosphatase complex, respectively, caused a marked upregulation of bacterial-induced antimicrobial peptide gene expression in both S2 cells and adult flies. Deregulated IMD signaling is associated with reduced lifespan of -deficient flies in the absence of any infection. In contrast, flies overexpressing this phosphatase are highly sensitive to bacterial infections. Altogether, our results highlight an evolutionarily conserved function of PP4c in the regulation of NF-κB signaling from to mammals.},
keywords = {Drosophila, IKK complex, IMD, immune response, M3i, matt, NF-κB, PP4 complex},
pubstate = {published},
tppubtype = {article}
}
The evolutionarily conserved immune deficiency (IMD) signaling pathway shields against bacterial infections. It regulates the expression of antimicrobial peptides encoding genes through the activation of the NF-κB transcription factor Relish. Tight regulation of the signaling cascade ensures a balanced immune response, which is otherwise highly harmful. Several phosphorylation events mediate intracellular progression of the IMD pathway. However, signal termination by dephosphorylation remains largely elusive. Here, we identify the highly conserved protein phosphatase 4 (PP4) complex as a bona fide negative regulator of the IMD pathway. RNA interference-mediated gene silencing of , , and which encode the catalytic and regulatory subunits of the phosphatase complex, respectively, caused a marked upregulation of bacterial-induced antimicrobial peptide gene expression in both S2 cells and adult flies. Deregulated IMD signaling is associated with reduced lifespan of -deficient flies in the absence of any infection. In contrast, flies overexpressing this phosphatase are highly sensitive to bacterial infections. Altogether, our results highlight an evolutionarily conserved function of PP4c in the regulation of NF-κB signaling from to mammals.
2017
Mussabekova Assel, Daeffler Laurent, Imler Jean-Luc
Innate and intrinsic antiviral immunity in Drosophila Article de journal
Dans: Cell. Mol. Life Sci., 2017, ISSN: 1420-9071.
Résumé | Liens | BibTeX | Étiquettes: Argonaute 2, Dicer-2, IMD pathway, imler, Jak/STAT pathway, M3i, NF-κB
@article{mussabekova_innate_2017,
title = {Innate and intrinsic antiviral immunity in Drosophila},
author = {Assel Mussabekova and Laurent Daeffler and Jean-Luc Imler},
doi = {10.1007/s00018-017-2453-9},
issn = {1420-9071},
year = {2017},
date = {2017-01-01},
journal = {Cell. Mol. Life Sci.},
abstract = {The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations.},
keywords = {Argonaute 2, Dicer-2, IMD pathway, imler, Jak/STAT pathway, M3i, NF-κB},
pubstate = {published},
tppubtype = {article}
}
The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations.