Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the <i>Drosophila</i> Immune Response

Wehbe, Layale Salem; Barakat, Dana; Acker, Adrian; Khoury, Rita; Reichhart, Jean‐Marc; Matt, Nicolas; Chamy, Laure El

doi:10.4049/jimmunol.1901497

Cited by 3 publications

(2 citation statements)

References 117 publications

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“…Similarly to ubiquitination, several phosphorylation reactions also play a pivotal role in IMD pathway signaling. Recently, our group published the identification of the protein phosphatase PP4 as a new negative regulator of the IMD pathway [ 91 ]. Inhibition of the components of the PP4 complex induced an over-activation of the IMD pathway, highlighted by a marked increase in AMP levels both in vitro and in vivo, which ultimately leads to a reduced lifespan of adult flies.…”

Section: Various Ways To Inactivate the Nf-κb Imd-relish Pathwaymentioning

confidence: 99%

“…Inhibition of the components of the PP4 complex induced an over-activation of the IMD pathway, highlighted by a marked increase in AMP levels both in vitro and in vivo, which ultimately leads to a reduced lifespan of adult flies. Conversely, flies over-expressing the negative regulator PP4 exhibit an impaired immune response and are not able to control Gram (-) bacterial infection [ 91 ]. The involvement of additional protein phosphatases in the regulation of the IMD pathway is quite likely and remains to be explored.…”

Section: Various Ways To Inactivate the Nf-κb Imd-relish Pathwaymentioning

confidence: 99%

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Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila

Cammarata-Mouchtouris

Acker

Goto

et al. 2022

Biomedicines

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Metazoans have developed strategies to protect themselves from pathogenic attack. These preserved mechanisms constitute the immune system, composed of innate and adaptive responses. Among the two kinds, the innate immune system involves the activation of a fast response. NF-κB signaling pathways are activated during infections and lead to the expression of timely-controlled immune response genes. However, activation of NF-κB pathways can be deleterious when uncontrolled. Their regulation is necessary to prevent the development of inflammatory diseases or cancers. The similarity of the NF-κB pathways mediating immune mechanisms in insects and mammals makes Drosophila melanogaster a suitable model for studying the innate immune response and learning general mechanisms that are also relevant for humans. In this review, we summarize what is known about the dynamic regulation of the central NF-κB-pathways and go into detail on the molecular level of the IMD pathway. We report on the role of the nuclear protein Akirin in the regulation of the NF-κB Relish immune response. The use of the Drosophila model allows the understanding of the fine-tuned regulation of this central NF-κB pathway.

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Section: Various Ways To Inactivate the Nf-κb Imd-relish Pathwaymentioning

confidence: 99%

Section: Various Ways To Inactivate the Nf-κb Imd-relish Pathwaymentioning

confidence: 99%

Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila

Cammarata-Mouchtouris

Acker

Goto

et al. 2022

Biomedicines

Self Cite

View full text Add to dashboard Cite

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The Intestinal Immune Defense System in Insects

Zeng

Jaffar

et al. 2022

IJMS

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Over a long period of evolution, insects have developed unique intestinal defenses against invasion by foreign microorganisms, including physical defenses and immune responses. The physical defenses of the insect gut consist mainly of the peritrophic matrix (PM) and mucus layer, which are the first barriers to pathogens. Gut microbes also prevent the colonization of pathogens. Importantly, the immune-deficiency (Imd) pathways produce antimicrobial peptides to eliminate pathogens; mechanisms related to reactive oxygen species are another important pathway for insect intestinal immunity. The janus kinase/STAT signaling pathway is involved in intestinal immunity by producing bactericidal substances and regulating tissue repair. Melanization can produce many bactericidal active substances into the intestine; meanwhile, there are multiple responses in the intestine to fight against viral and parasitic infections. Furthermore, intestinal stem cells (ISCs) are also indispensable in intestinal immunity. Only the coordinated combination of the intestinal immune defense system and intestinal tissue renewal can effectively defend against pathogenic microorganisms.

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CG4968 positively regulates the immune deficiency pathway by targeting Imd protein in Drosophila

Li¹,

Zhang²,

Zhang³

et al. 2023

PeerJ

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Drosophila melanogaster relies solely on innate immunity to defend against various microbial pathogens. Although it is well-known that the adaptor protein Imd undergoes K63-linked ubiquitination to activate the downstream signaling cascades, its involvement with K48-linked ubiquitination and what is responsible for controlling this modification remain largely unknown. In this study, we explored the immunological function of CG4968, which encodes a typical ovarian tumour-associated protease (OTU)-type deubiquitinase (Dub) in flies. Our in vitro and vivo evidence demonstrated that CG4968 plays a positive role in governing the immune deficiency (IMD), but not the Toll innate immune response in an OTU domain-dependent manner. Mechanistically, we found that CG4968 is associated with Imd to restrict its K48-linked ubiquitination, thereby contributing to its turnover. Collectively, our study uncovered a novel regulatory mechanism involving the K48-linked ubiquitination of Imd in Drosophila innate immunity.

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Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the Drosophila Immune Response

Abstract: https://anr.fr/) as part of the Investments for the Future program and a European Research Council (https://erc.europa.eu/) Advanced Grant (AdG_20090506 "Immudroso" to J.-M.R.

Cited by 3 publications

References 117 publications

Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila

Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila

The Intestinal Immune Defense System in Insects

CG4968 positively regulates the immune deficiency pathway by targeting Imd protein in Drosophila

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