Intramacrophage ROS Primes the Innate Immune System via JAK/STAT and Toll Activation

Chakrabarti, Sveta; Visweswariah, Sandhya S.

doi:10.1016/j.celrep.2020.108368

Cited by 85 publications

(106 citation statements)

References 61 publications

(67 reference statements)

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“…These observations suggest that specific aquaporins located in the somato-dendritic compartment of motoneurons act as conduits that facilitate entry of extracellular H 2 O 2 into the cytoplasm, where it can modulate dendritic growth pathways. This model is similar to one recently proposed by Chakrabarti and Visweswariah (2020) in Drosophila hemocytes, where in response to wounding Duox is activated, generates extracellular H 2 O 2 , which partly signals in an autocrine fashion with import back into the FIGURE 3 | Cell-specific expression of extracellular catalase produces a dendritic overgrowth phenotype comparable to that produced by UAS-bib.RNAi or UAS-Drip.RNAi expression. (A) Maximum intensity z-projections of representative RP2 motoneurons, from young third instar larvae raised at 25 • C and dissected 48 h after larval hatching.…”

Section: Discussionsupporting

confidence: 74%

“…Under conditions of cellautonomous neuronal overactivation, targeted co-expression of UAS-bib.RNAi (Djiane et al, 2013) or UAS-Drip.RNAi (Bergland et al, 2012) transgenes resulted in a significant abrogation of activity-induced arbor reduction, similar to co-expression of UAS-dDuox.RNAi (Figures 2A-C). In contrast, targeted co-expression of UAS-Prip.RNAi (Chakrabarti and Visweswariah, 2020) transgenes did not affect the UAS-dTrpA1 mediated reduction of dendritic arbors, nor did UAS-Prip.RNAi expression by itself have a measurable impact on dendritic development in absence of TrpA1-mediated over-activation. In contrast, mis-expression of UAS-bib.RNAi or UAS-Drip.RNAi alone, without concomitant dTrpA1 activity manipulation, was not phenotypically neutral, but produced a dendritic overgrowth phenotype, of increased dendritic length (Figure 2B) and branching complexity (Figure 2C) in the ventral part of the arbor.…”

Section: Aquaporin Channel Proteins Bib and Dripmentioning

confidence: 77%

“…hemocyte cytoplasm facilitated by the aquaporin Prip. Moreover, expression of a secreted Catalase, IRC, modulates such H 2 O 2 signaling (Chakrabarti and Visweswariah, 2020).…”

Section: Discussionmentioning

confidence: 99%

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Reactive Oxygen Species Mediate Activity-Regulated Dendritic Plasticity Through NADPH Oxidase and Aquaporin Regulation

Dhawan

Myers

Bailey

et al. 2021

Front. Cell. Neurosci.

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Neurons utilize plasticity of dendritic arbors as part of a larger suite of adaptive plasticity mechanisms. This explicitly manifests with motoneurons in the Drosophila embryo and larva, where dendritic arbors are exclusively postsynaptic and are used as homeostatic devices, compensating for changes in synaptic input through adapting their growth and connectivity. We recently identified reactive oxygen species (ROS) as novel plasticity signals instrumental in this form of dendritic adjustment. ROS correlate with levels of neuronal activity and negatively regulate dendritic arbor size. Here, we investigated NADPH oxidases as potential sources of such activity-regulated ROS and implicate Dual Oxidase (but not Nox), which generates hydrogen peroxide extracellularly. We further show that the aquaporins Bib and Drip, but not Prip, are required for activity-regulated ROS-mediated adjustments of dendritic arbor size in motoneurons. These results suggest a model whereby neuronal activity leads to activation of the NADPH oxidase Dual Oxidase, which generates hydrogen peroxide at the extracellular face; aquaporins might then act as conduits that are necessary for these extracellular ROS to be channeled back into the cell where they negatively regulate dendritic arbor size.

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Section: Discussionsupporting

confidence: 74%

Section: Aquaporin Channel Proteins Bib and Dripmentioning

confidence: 77%

See 1 more Smart Citation

Reactive Oxygen Species Mediate Activity-Regulated Dendritic Plasticity Through NADPH Oxidase and Aquaporin Regulation

Dhawan

Myers

Bailey

et al. 2021

Front. Cell. Neurosci.

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“…Research in Drosophila suggests that the characteristics of macrophages are changed following priming by an immune encounter, such as phagocytosis of apoptotic cells ( Weavers et al, 2016 ; Nonaka et al, 2017 ; Roddie et al, 2019 ; Chakrabarti and Visweswariah, 2020 ). This interaction leads to “immune training”, consisting of changes in intracellular signaling and the repertoire of phagocytic receptors, which can determine behavior in future encounters ( Weavers et al, 2016 ; Nonaka et al, 2017 ; Roddie et al, 2019 ; Chakrabarti and Visweswariah, 2020 ). Consistent with this, a study provided molecular evidence of Drosophila macrophages taking on an alternatively activated (M2) status in response to local cues in tissue regeneration ( Neves et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Macrophages and Their Organ Locations Shape Each Other in Development and Homeostasis – A Drosophila Perspective

Mase

Augsburger

Brückner

2021

Front. Cell Dev. Biol.

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Across the animal kingdom, macrophages are known for their functions in innate immunity, but they also play key roles in development and homeostasis. Recent insights from single cell profiling and other approaches in the invertebrate model organism Drosophila melanogaster reveal substantial diversity among Drosophila macrophages (plasmatocytes). Together with vertebrate studies that show genuine expression signatures of macrophages based on their organ microenvironments, it is expected that Drosophila macrophage functional diversity is shaped by their anatomical locations and systemic conditions. In vivo evidence for diverse macrophage functions has already been well established by Drosophila genetics: Drosophila macrophages play key roles in various aspects of development and organogenesis, including embryogenesis and development of the nervous, digestive, and reproductive systems. Macrophages further maintain homeostasis in various organ systems and promote regeneration following organ damage and injury. The interdependence and interplay of tissues and their local macrophage populations in Drosophila have implications for understanding principles of organ development and homeostasis in a wide range of species.

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“…A recent study in Drosophila revealed that of H 2 O 2 produced from a wound lead to the activation of hemocytes, which are the equivalent of macrophages in fly. This activation is characterized by the activation of Toll signaling and the induction of the cytokine-like protein upd3, through the action of the Tyrosin-protein Kinase Src42A, the Drosophila Lyn homolog ( 83 ). We propose that early wound signals may play a conserved role in macrophage polarization in arthropods and vertebrates during wound healing, as ancient triggers of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Damage-Induced Calcium Signaling and Reactive Oxygen Species Mediate Macrophage Activation in Zebrafish

et al. 2021

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Immediately after a wound, macrophages are activated and change their phenotypes in reaction to danger signals released from the damaged tissues. The cues that contribute to macrophage activation after wounding in vivo are still poorly understood. Calcium signaling and Reactive Oxygen Species (ROS), mainly hydrogen peroxide, are conserved early wound signals that emanate from the wound and guide neutrophils within tissues up to the wound. However, the role of these signals in the recruitment and the activation of macrophages is elusive. Here we used the transparent zebrafish larva as a tractable vertebrate system to decipher the signaling cascade necessary for macrophage recruitment and activation after the injury of the caudal fin fold. By using transgenic reporter lines to track pro-inflammatory activated macrophages combined with high-resolutive microscopy, we tested the role of Ca²⁺ and ROS signaling in macrophage activation. By inhibiting intracellular Ca²⁺ released from the ER stores, we showed that macrophage recruitment and activation towards pro-inflammatory phenotypes are impaired. By contrast, ROS are only necessary for macrophage activation independently on calcium. Using genetic depletion of neutrophils, we showed that neutrophils are not essential for macrophage recruitment and activation. Finally, we identified Src family kinases, Lyn and Yrk and NF-κB as key regulators of macrophage activation in vivo, with Lyn and ROS presumably acting in the same signaling pathway. This study describes a molecular mechanism by which early wound signals drive macrophage polarization and suggests unique therapeutic targets to control macrophage activity during diseases.

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Intramacrophage ROS Primes the Innate Immune System via JAK/STAT and Toll Activation

Cited by 85 publications

References 61 publications

Reactive Oxygen Species Mediate Activity-Regulated Dendritic Plasticity Through NADPH Oxidase and Aquaporin Regulation

Reactive Oxygen Species Mediate Activity-Regulated Dendritic Plasticity Through NADPH Oxidase and Aquaporin Regulation

Macrophages and Their Organ Locations Shape Each Other in Development and Homeostasis – A Drosophila Perspective

Damage-Induced Calcium Signaling and Reactive Oxygen Species Mediate Macrophage Activation in Zebrafish

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