Inflammatory production of reactive oxygen species by Drosophila hemocytes activates cellular immune defenses

Myers, Amber L.; Harris, Caitlin; Choe, Kwang Min; Brennan, Catherine A.

doi:10.1016/j.bbrc.2018.09.126

Cited by 45 publications

(38 citation statements)

References 36 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasmatocytes also showed increased expression of many genes involved in the oxidative stress response, notably many glutathione S transferase genes and other detoxifying enzymes such as peroxidasin (FC 15.51), superoxide dismutases 1 and 2 (FCs: 2.8 and 3.5) or thioredoxin peroxidase 1 and 2 (FC: 2 and 2.4). These genes may play a role in immune response activation [80]. In parallel, we observed an increase in gene transcripts involved in other cellular stress pathways, e.g.…”

Section: Plos Onesupporting

confidence: 62%

Comparative RNA-Seq analyses of Drosophila plasmatocytes reveal gene specific signatures in response to clean injury and septic injury

2020

View full text Add to dashboard Cite

Drosophila melanogaster's blood cells (hemocytes) play essential roles in wound healing and are involved in clearing microbial infections. Here, we report the transcriptional changes of larval plasmatocytes after clean injury or infection with the Gram-negative bacterium Escherichia coli or the Gram-positive bacterium Staphylococcus aureus compared to hemocytes recovered from unchallenged larvae via RNA-Sequencing. This study reveals 676 differentially expressed genes (DEGs) in hemocytes from clean injury samples compared to unchallenged samples, and 235 and 184 DEGs in E. coli and S. aureus samples respectively compared to clean injury samples. The clean injury samples showed enriched DEGs for immunity, clotting, cytoskeleton, cell migration, hemocyte differentiation, and indicated a metabolic reprogramming to aerobic glycolysis, a well-defined metabolic adaptation observed in mammalian macrophages. Microbial infections trigger significant transcription of immune genes, with significant differences between the E. coli and S. aureus samples suggesting that hemocytes have the ability to engage various programs upon infection. Collectively, our data bring new insights on Drosophila hemocyte function and open the route to post-genomic functional analysis of the cellular immune response.

show abstract

Section: Plos Onesupporting

confidence: 62%

Comparative RNA-Seq analyses of Drosophila plasmatocytes reveal gene specific signatures in response to clean injury and septic injury

2020

View full text Add to dashboard Cite

show abstract

“…Macrophage-like plasmatocytes are involved in the phagocytosis and encapsulation of pathogens ( Fauvarque and Williams, 2011 ). Upon infection, a biphasic ROS response occurs ( Myers et al, 2018 ). Initially, upon stimulation, all hemocytes, including non-phagocytic prohemocytes and crystal cells, mount a transient ROS response, which, in turn, influences plasmatocyte activation.…”

Section: Ros Formation In Different Speciesmentioning

confidence: 99%

From Flies to Men: ROS and the NADPH Oxidase in Phagocytes

Moghadam

Henneke

Kolter

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The cellular formation of reactive oxygen species (ROS) represents an evolutionary ancient antimicrobial defense system against microorganisms. The NADPH oxidases (NOX), which are predominantly localized to endosomes, and the electron transport chain in mitochondria are the major sources of ROS. Like any powerful immunological process, ROS formation has costs, in particular collateral tissue damage of the host. Moreover, microorganisms have developed defense mechanisms against ROS, an example for an arms race between species. Thus, although NOX orthologs have been identified in organisms as diverse as plants, fruit flies, rodents, and humans, ROS functions have developed and diversified to affect a multitude of cellular properties, i.e., far beyond direct antimicrobial activity. Here, we focus on the development of NOX in phagocytic cells, where the so-called respiratory burst in phagolysosomes contributes to the elimination of ingested microorganisms. Yet, NOX participates in cellular signaling in a cell-intrinsic and -extrinsic manner, e.g., via the release of ROS into the extracellular space. Accordingly, in humans, the inherited deficiency of NOX components is characterized by infections with bacteria and fungi and a seemingly independently dysregulated inflammatory response. Since ROS have both antimicrobial and immunomodulatory properties, their tight regulation in space and time is required for an efficient and well-balanced immune response, which allows for the reestablishment of tissue homeostasis. In addition, distinct NOX homologs expressed by non-phagocytic cells and mitochondrial ROS are interlinked with phagocytic NOX functions and thus affect the overall redox state of the tissue and the cellular activity in a complex fashion. Overall, the systematic and comparative analysis of cellular ROS functions in organisms of lower complexity provides clues for understanding the contribution of ROS and ROS deficiency to human health and disease.

show abstract

“…Since Tak1-mediated JNK activation is transient, lasting less than one hour [48], the observed JNK activation (lasting at least 3-7 dpi) is probably due to an IMD-independent activation. Upon oxidative stress, the JNK pathway is induced through p53 upregulation of Traf4 that then phosphorylates Hep [49][50][51]. Activated JNK pathway then induces other oxidative stressassociated genes, such as FoxO and κ-B Ras (AAEL003817) [52].…”

Section: Plos Pathogensmentioning

confidence: 99%

JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

et al. 2020

View full text Add to dashboard Cite

Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N-terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apoptosis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbovirus transmission.

show abstract

Inflammatory production of reactive oxygen species by Drosophila hemocytes activates cellular immune defenses

Cited by 45 publications

References 36 publications

Comparative RNA-Seq analyses of Drosophila plasmatocytes reveal gene specific signatures in response to clean injury and septic injury

Comparative RNA-Seq analyses of Drosophila plasmatocytes reveal gene specific signatures in response to clean injury and septic injury

From Flies to Men: ROS and the NADPH Oxidase in Phagocytes

JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

Contact Info

Product

Resources

About