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

Abstract

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.

Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling

“…Whether glia engage in other pro-inflammatory signaling remains unclear, although Imd signaling has been reported in glia 7,39 . While we did not see elevated expression of AttA in glia in the drpr ∆5 mutant, Relish regulates the expression of many genes including other AMPs 17 . Identification of these key transcriptional targets of Relish will provide insight into how local and systemic inflammation drives neuroinflammation and neurodegeneration in Drosophila .…”

“…While AMPs are known to target bacteria and fungi, they have also been shown to contribute to neurodegeneration and other processes 5,7 . Moreover, the Toll and Imd pathways activate transcription of other genes, are expressed in multiple tissues and act in concert with other pathways and phagocytic cells to remove invading pathogens 5,17 .…”

“…The humoral immune response in Drosophila is mediated primarily by two NFkB signaling pathways, Toll and Immune deficiency (Imd) 5,6,17 . These pathways activate transcription of antimicrobial peptides (AMPs) primarily in the fat body, a tissue with similarities to the vertebrate liver.…”

Transcriptional survey of ovarian bacteriomes in the cereal weevil,Sitophilus oryzae, shows down-regulation of immune effectors at the onset of sexual maturity

“…Many negative regulators of the IMD pathway have been characterized in other insects, especially the genetic model Drosophila melanogaster (Zhang et al, 2021; Cammarata-Mouchtouris et al, 2022). Analysis of their expression patterns between D1 and D7 in the germarium suggests the potential implication of three main regulatory mechanisms in this tissue.…”

“…Many negative regulators of the IMD pathway have been characterized in other insects, especially the genetic model Drosophila melanogaster (Zhang et al, 2021;Cammarata-Mouchtouris et al, 2022).…”